Risks Of Anticoagulant Therapy Research Articles

Analysis of factors related to recanalization of portal vein thrombosis in liver cirrhosis: a retrospective cohort study

BackgroundPortal vein thrombosis (PVT) is a common complication of liver cirrhosis, yet there are fewer studies about predictors of PVT recanalization. We aimed to further explore the predictors of recanalization in cirrhotic PVT to facilitate accurate prediction of patients’ clinical status and timely initiation of appropriate treatment and interventions. To further investigate the benefits and risks of anticoagulant therapy in cirrhotic PVT patients.MethodsA retrospective cohort study of patients with cirrhotic PVT in our hospital between January 2016 and December 2022, The primary endpoint was to analyze predictors of PVT recanalization by COX regression. Others included bleeding rate, liver function, and mortality.ResultsThis study included a total of 82 patients, with 30 in the recanalization group and 52 in the non-recanalization group. Anticoagulation therapy was the only independent protective factor for portal vein thrombosis recanalization and the independent risk factors included massive ascites, history of splenectomy, Child-Pugh B/C class, and main trunk width of the portal vein. Anticoagulation therapy was associated with a significantly higher rate of PVT recanalization (75.9% vs. 20%, log-rank P < 0.001) and a lower rate of PVT progression (6.9% vs. 54.7%, log-rank P = 0.002). There was no significant difference between different anticoagulation regimens for PVT recanalization. Anticoagulation therapy did not increase the incidence of bleeding complications(P = 0.407). At the end of the study follow-up, Child-Pugh classification, MELD score, and albumin level were better in the anticoagulation group than in the non-anticoagulation group. There was no significant difference in 2-year survival between the two groups.ConclusionAnticoagulation, massive ascites, history of splenectomy, Child-Pugh B/C class, and main portal vein width were associated with portal vein thrombosis recanalization. Anticoagulation may increase the rate of PVT recanalization and decrease the rate of PVT progression without increasing the rate of bleeding. Anticoagulation may be beneficial in improving liver function in patients with PVT in cirrhosis.

#1912 Assessment of the dynamics of renal anemia in patients with atrial fibrillation and chronic kidney disease stage IIIb-V during anticoagulant therapy

Abstract Background and Aims Therapy with oral anticoagulants prevents the development of most ischemic strokes and systemic embolisms in patients with atrial fibrillation (AF) and chronic kidney disease (CKD), and also helps to increase life expectancy, improving its quality. It should be emphasized that with CKD, the risk of hemorrhagic complications also increases, which in turn can lead to the progression of renal anemia and deterioration in the patient's general condition. The main complication of anticoagulants is an increased risk of major bleeding, including intracranial, life-threatening bleeding. The purpose of the study is to assess the benefits and risks of anticoagulant therapy in patients with renal anemia in AF and stage IIIb-V CKD. Method From February 2022 to July 2023, 2983 patients with AF were admitted to cardiology departments. The majority of patients with AF had hypertension (94%), chronic heart failure (71%), coronary heart disease (65%), and type 2 diabetes mellitus (23%). CKD was diagnosed according to KDIGO criteria, glomerular filtration rate (GFR) was calculated using the CKD-EPI formula. Indications for anticoagulant therapy (ACT) were determined according to European guidelines for AF using the scales for assessing the risk of thromboembolic complications (TEC)—CHA2DS2-VASc and the risk of bleeding—HAS-BLED. Results GFR up to 45 ml/min/1.73 m2 was detected in 2189 (73%) patients with AF, GFR less than 45 ml/min/1.73 m2 in 794 (27%) patients with AF (CKD stages IIIb–V in 516 (65%) cases, for the first identified sustained decrease in glomerular filtration rate (FISD in GFR) of less than 45 ml/min/1.73 m2 was detected in 278 (35%) cases). Among patients with AF and CKD, renal anemia was diagnosed in 23% of cases, in 63% (n = 505) of cases with AF and GFR &amp;lt;45 ml/min/1.73 m2. With a GFR of 45-30 ml/min/1.73 m2, renal anemia was detected in 59%, with a GFR of 30-15 ml/min/1.73 m2—in 89%, with a GFR &amp;lt;15 ml/min/1.73 m2—in 97%, with FISD in GFR &amp;lt;45 ml/min/1.73 m2—in 51%. When stratifying thromboembolic risk according to the CHA2DS2-VASc scale in patients with AF and CKD stages IIIb–V, 0-1 points were scored by 1% (n = 11), 2-5 points by 53% (n = 420), ≥6 points by 46% (n = 363) patients. The results of the analysis of the risk of bleeding according to the HAS-BLED scale showed the following data: 0-1 point—8% (n = 64), 2 points—15% (n = 118), ≥3 points—77% (n = 612). When studying the frequency of ACT prescription, it was revealed that rivaroxaban was prescribed in 21%, apixaban—22%, dabigatran—10%, warfarin—25%, low molecular weight heparins—3%, ACT not recommended—9%, ACT of choice—10% of cases (Table 1). In mild renal anemia (in 39% of patients), taking ACT led to a reduction in the risk of developing TEC—RR 0.55 with 95% CI 0.38-0.79; in case of moderate renal anemia (in 47.3% of patients), the risk of TEC did not decrease RR 1.03 with 95% CI 0.69-1.58; with severe renal anemia (in 13.7% of patients), the risk of TEC was also not reduced—RR 1.6 with 95% CI 1.17-2.2). Conclusion Every fourth patient in the cardiology department with AF showed a decrease in GFR &amp;lt;45 ml/min/1.73 m2, while 1/3 of them had FISD in GFR &amp;lt;45 ml/min/1.73 m2, and it is in these patients that the most common the dose of the prescribed anticoagulant did not correspond to the GFR; 50% of patients with GFR &amp;lt;45 ml/min/1.73 m2 and 32% with GFR &amp;lt;30 ml/min/1.73 m2 are recommended to use direct oral anticoagulants. Patients with stage V CKD were not prescribed direct oral anticoagulants; in 50% of cases, none of the anticoagulants was recommended.

Comparative effectiveness of warfarin in cirrhotic patients with non-symptomatic portal vein thrombosis: a multicenter, randomized controlled trial

ABSTRACT The effectiveness and risks of anticoagulant therapy in cirrhotic patients with non-symptomatic portal vein thrombosis (PVT) remain unclear. We conducted a multicenter, Zelen-designed randomized controlled trial to determine the effectiveness of warfarin in cirrhotic patients with non-symptomatic PVT during a one-year follow-up. In brief, 64 patients were 1:1 randomly divided into the anticoagulation group or the untreated group. The probability of recanalization was significantly higher in the anticoagulation group than those untreated in both ITT analysis (71.9% vs 34.4%, p = 0.004) and PP analysis (76.7% vs 32.4%, p < 0.001). Anticoagulation treatment was the independent predictor of recanalization (HR 2.776, 95%CI 1.307–5.893, p = 0.008). The risk of bleeding events and mortality were not significantly different. A significantly higher incidence of ascites aggravation was observed in the untreated group (3.3% vs 26.5%, p = 0.015). In conclusion, warfarin was proved to be an effective and safe as an anticoagulation therapy for treating non-symptomatic PVT in cirrhotic patients.

Clinical benefits and risks of anticoagulation therapy according to the degree of chronic kidney disease in patients with atrial fibrillation

BackgroundThe clinical benefits and risks of anticoagulation therapy in patients with chronic kidney disease (CKD) are still inconclusive. We describe the outcomes of patients with atrial fibrillation (AF) after anticoagulation therapy according to differences in creatinine clearance (CrCl). We also aimed to determine the patients who could benefit from anticoagulation therapy.MethodsThis is a retrospective observational review of patients with AF who were managed at Asan Medical Center (Seoul, Korea) between January 1, 2006, and December 31, 2018. Patients were categorized into groups according to their baseline CrCl by Cockcroft–Gault equation and their outcomes were evaluated (CKD 1, ≥ 90 mL/min; CKD2, 60–89 mL/min; CKD3, 30–59 mL/min; CKD4, 15–29 mL/min; CKD 5, < 15 mL/min). The primary outcome was NACE (net adverse clinical events), defined as a composite of all-cause mortality, thromboembolic events, and major bleeding.ResultsWe identified 12,714 consecutive patients with AF (mean 64.6 ± 11.9 years, 65.3% male, mean CHA2DS2-VASc score 2.4 ± 1.6 points) between 2006 and 2017. In patients receiving anticoagulation therapy (n = 4447, 35.0%), warfarin (N = 3768, 84.7%) was used more frequently than NOACs (N = 673, 15.3%). There was a higher 3-year rate of NACE with renal function deterioration (14.8%, 18.6%, 30.3%, 44.0%, and 48.8% for CKD stages 1–5, respectively).The clinical benefit of anticoagulation therapy was most prominent in patients with CKD 1 (hazard ratio [HR] 0.49, 95% confidence interval [CI] 0.37–0.67), 2 (HR 0.64 CI 0.54–0.76), and 3 (HR 0.64 CI 0.54–0.76), but not in CKD 4 (HR 0.86, CI 0.57–1.28) and 5 (HR 0.81, CI 0.47–1.40). Among patients with CKD, the benefit of anticoagulation therapy was only evident in those with a high risk of embolism (CHA2DS2-VASc score ≥ 4, HR 0.25, CI 0.08–0.80).ConclusionAdvanced CKD is associated with a higher risk of NACE. The clinical benefit of anticoagulation therapy was reduced with the increasing CKD stage.

Thrombosis and Anticoagulation Strategies in Patients with COVID-19 Including Japanese Perspective.

Coronavirus disease 2019 (COVID-19) has become a major health problem worldwide since 2020. Although the main pathophysiology of COVID-19 is a respiratory infectious disease, it could also cause cardiovascular complications, including thrombosis. Thus, anticoagulation therapy has been thought to help prevent thrombosis, leading to improved survival. However, to date, several aspects of the optimal anticoagulation strategies for COVID-19 remain unclear. Considering the status of COVID-19-related thrombosis and some domestic issues in Japan, the optimal anticoagulation strategies for COVID-19 might have to be based on Japanese domestic clinical data considering racial difference. Racial disparities in terms of thromboembolic risk have been well known in the pre-COVID-19 era, and the risk of COVID-19-associated thrombosis depending on race could be an important issue. Considering a potential higher risk of bleeding with anticoagulation therapy in the Asian population, it might be important to maintain a good balance between the risks of thrombosis and bleeding. Latest evidences of COVID-19-related thrombosis and anticoagulation strategies, including some domestic issues in Japan, showed a different status of COVID-19-related thrombosis in Japan from that in Western countries, suggesting the potential benefit of different anticoagulation strategies, specifically for the Japanese population. Although these insights could be useful for the consideration of anticoagulation strategies for the Japanese population, the final decision should be based on balancing the benefits and risks of anticoagulation therapy in each patient.

Abstract P649: Extracranial Hemorrhage in the Setting of Gastrointestinal Or Genitourinary Cancer is Associated With Increased Risk of Ischemic Stroke in Patients With Atrial Fibrillation

Background and Purpose: Anticoagulation therapy reduces the risk for ischemic stroke in atrial fibrillation (AF) but also predisposes patients to hemorrhagic complications. Patients with GI or GU cancer and AF are at higher risk of bleeding complications with anticoagulation therapy. There is limited knowledge on the risk of first-ever ischemic stroke in AF patients after extracranial hemorrhage (ECH) in patients with gastrointestinal or genitourinary (GI/GU) cancer. Methods: We conducted a retrospective study using the California State Inpatient Database (SID) including all non-federal hospital admissions in California from 2005-2011. The exposure variable was hospitalization with a diagnosis of ECH with a previous diagnosis of AF. The outcome variable was a subsequent hospitalization with acute ischemic stroke. We excluded patients with stroke prior to or at the time of ECH diagnosis. We calculated adjusted hazard ratios (HRs) for ischemic stroke during follow up and at 6-month intervals using Cox regression models adjusted for pertinent demographics and co-morbidities and stratifying patients with ECH based on the presence/absence of a GI/GU cancer. Results: We identified 764,257 AF patients (mean age 75 years, 49% women) without a documented history of stroke. Of these, 98,647 (13%) had an ECH-associated hospitalization, and 22,748 patients (3%) developed an ischemic stroke during a mean follow up. Compared to non-ECH patients, patients with ECH in the setting of a GI/GU cancer had a significantly higher risk of incident ischemic stroke (adjusted HR 1.40, 95% CI 1.20-1.64).Whereas there was only a modest increase in ischemic stroke risk in those without GI/GU cancer (adjusted HR 1.09 95% CI 1.05-1.13). Conclusion: AF patients hospitalized with ECH in the setting of GI/GU cancer have a particularly high risk of incident ischemic stroke. Particular consideration should be given to the optimal balance between the benefits and risks of anticoagulation therapy and the use of non-anticoagulant alternatives such as left atrial appendage closure in this vulnerable population.

Risk of Ischemic Stroke in Patients With Atrial Fibrillation After Extracranial Hemorrhage.

Anticoagulation therapy not only reduces the risk of ischemic stroke in atrial fibrillation (AF) but also predisposes patients to hemorrhagic complications. There is limited knowledge on the risk of first-ever ischemic stroke in patients with AF after extracranial hemorrhage (ECH). We conducted a retrospective study using the California State Inpatient Database including all nonfederal hospital admissions in California from 2005 to 2011. The exposure variable was hospitalization with a diagnosis of ECH with a previous diagnosis of AF. The outcome variable was a subsequent hospitalization with acute ischemic stroke. We excluded patients with stroke before or at the time of ECH diagnosis. We calculated adjusted hazard ratios for ischemic stroke during follow-up and at 6-month intervals using Cox regression models adjusted for pertinent demographics and comorbidities. In subgroup analyses, subjects were stratified by primary ECH diagnosis, severity/type of ECH, age, CHA2DS2-VASc score, or the presence/absence of a gastrointestinal or genitourinary cancer. We identified 764 257 patients with AF (mean age 75 years, 49% women) without a documented history of stroke. Of these, 98 647 (13%) had an ECH-associated hospitalization, and 22 748 patients (3%) developed an ischemic stroke during the study period. Compared to patients without ECH, subjects with ECH had ≈15% higher rate of ischemic stroke (overall adjusted hazard ratio, 1.15 [95% CI, 1.11-1.19]). The risk appeared to remain elevated for at least 18 months after the index ECH. In subgroup analyses, the risk was highest in subjects with a primary admission diagnosis of ECH, severe ECH, gastrointestinal-type ECH, with gastrointestinal or genitourinary cancer, and age ≥60 years. Patients with AF hospitalized with ECH may have a slightly elevated risk for future ischemic stroke. Particular consideration should be given to the optimal balance between the benefits and risks of anticoagulation therapy and the use of nonanticoagulant alternatives, such as left atrial appendage closure in this vulnerable population.

General Population vs. Patient Preferences in Anticoagulant Therapy: A Discrete Choice Experiment.

Preference weights derived from general population samples are often used for therapeutic decision making. In contrast, patients with cardiovascular disease may have different preferences concerning the benefits and risks of anticoagulant therapy. Using a discrete choice experiment, we compared preferences for anticoagulant treatment outcomes between the general population and patients with cardiovascular disease. A sample of the general US population and a sample of patients with cardiovascular disease were selected from online panels. We used a discrete choice experiment questionnaire to elicit preferences in both populations concerning treatment benefits and risks. Seven attributes described hypothetical treatments: non-fatal stroke, non-fatal myocardial infarction, cardiovascular death, minor bleeding, major bleeding, fatal bleeding, and the need for monitoring. We measured preference weights and maximum acceptable risks in both populations. A total of 352 individuals from the general population and 341 patients completed the questionnaire. After propensity score matching, 284 from each group were included in the analysis. On average, the general population members valued a 1% increased risk of fatal bleeding as being the same as a 4.2% increase in a non-fatal myocardial infarction, a 2.8% increase in cardiovascular death, or a 14.1% increase in minor bleeding. Patients, in contrast, perceived a 1% increased risk of fatal bleeding as being the same as a 2.0% increase in a non-fatal myocardial infarction, a 3.2% increase in cardiovascular death, and a 16.7% increase in minor bleeding. The general population and patients with cardiovascular disease had slightly different preferences for treatment outcomes. The differences can potentially influence estimated benefits and risks and patient-centered treatment decisions.

Risk of anticoagulation therapy in surgical intensive care unit patients predicted by thromboelastograph

To explore the correlation between thromboelastography (TEG) parameters and the risk of venous thromboembolism (VTE) and bleeding in patients receiving anticoagulant therapy in surgical intensive care unit (SICU). 205 patients received low molecular weight heparin (LMWH) anticoagulant therapy admitted to SICU of Tianjin Hospital from December 2016 to December 2017 were consecutively enrolled. TEG detection was performed in all patients at 1 day after anticoagulation therapy, and coagulation reaction time (R value), blood clot generation time (K value), blood clot generation rate (α angle) and maximum width value (MA value) were recorded. At the same time, the traditional coagulation function test was carried out, and prothrombin time (PT), activated partial thromboplastin time (APTT) and D-dimer levels were also recorded. The incidence of deep venous thrombosis (DVT), pulmonary embolism (PE) and bleeding during hospitalization were observed. Multivariate Logistic regression analysis was used to analyze the risk factors for VTE and bleeding in patients receiving anticoagulant therapy. Of 205 patients, during the anticoagulant treatment, 14 patients developed DVT, and 4 patients with PE (2 of them were combined with DVT) with an incidence of 7.8% (16/205). There were 2 patients suffering from cerebral hemorrhage, 2 patients with gastric bleeding, and 1 patient with intra-tracheal hemorrhage with an incidence of 2.4% (5/205). Compared with the patients without VTE or bleeding, the R value of TEG in patients with VTE was significantly lowered (minutes: 4.6±2.2 vs. 7.4±1.4, P < 0.01), which was significantly increased in patients with hemorrhagic complications (minutes: 12.1±1.1 vs. 7.4±1.4, P < 0.01). There was no significant difference in the K value, α angle, MA value of TEG, or PT, APTT, D-dimer between the patients with and without VTE or bleeding. Multivariate Logistic regression analysis revealed that the R value of TEG was independent risk factor for incidence of VTE and hemorrhagic complication in SICU patients who receiving anticoagulation therapy [VTE: β = 0.386, odds ratio (OR) = 1.096, 95% confidence interval (95%CI) = 1.021-2.361, P = 0.006; hemorrhagic complication: β = -1.213, OR = 1.051, 95%CI = 1.017-3.458, P = 0.045]. The R value of TEG is associated with the occurrence of VTE and hemorrhagic complications in patients receiving anticoagulant therapy in SICU.

Patients' preferences in anticoagulant therapy: discrete choice experiment.

With proliferating treatment options for anticoagulant therapy, physicians and patients must choose among them based on their benefits and risks. Using a Discrete Choice Experiment, we elicited patients' relative preferences for specific benefits and risks of anticoagulant therapy. We selected a sample of US patients with cardiovascular disease from an online panel and elicited their preferences for benefits and risks of anticoagulant therapy: nonfatal stroke, nonfatal myocardial infarction, cardiovascular death, minor bleeding, major bleeding, bleeding death, and need for monitoring. These attributes were used to design scenarios describing hypothetical treatments that were labeled as new drug, old drug, or no drug. Latent class analysis was used to identify groups of patients with similar preferences. A total of 341 patients completed all Discrete Choice Experiment questions. On average, patients valued a 1% increased risk of a fatal bleeding event the same as a 2% increase in nonfatal myocardial infarction, a 3% increase in nonfatal stroke, a 3% increase in cardiovascular death, a 6% increase in major bleeding, and a 16% increase in minor bleeding. The odds of choosing no drug or old drug versus new drug were 0.72 (95% confidence interval, 0.61-0.84) and 0.86 (95% confidence interval, 0.81-0.93), respectively. Previous stroke or myocardial infarction was associated with membership in the class with larger negative preferences for these outcomes. Patients' preferences for various outcomes of anticoagulant therapy vary and depend on their previous experiences with myocardial infarction or stroke. Incorporating these preferences into benefit risk calculation and treatment decisions can enhance patient-centered care.

Diverging opinions about shared decisions.

Shared decision making is an emerging physician-patient interaction model for clinical practice [1]. Essentially, shared decision making implies that both the physician and the patient contribute to and bear responsibility for the clinical decision to be taken. It offers an alternative for the paternalistic model, in which it is the physician who informs the patient and proposes the decision to be made. Shared decision making emphasizes patient’s autonomy and recognizes the argumentation and preferences of the informed patient as valid elements in the decision process. Thus, it can dramatically influence the physician-patient relationship. E.g., in a given case, the choice for doing nothing as an alternative for pharmacotherapy could be considered as an acceptable outcome of the shared decision making process, while it could be considered as disobedient behavior of the patient in the paternalistic model. Clinical practice guidelines usually define a single best option in a given case [2]. Seen from this perspective, guidelines leave little freedom for the patient and reinforce the paternalistic model rather than shared decision making. Moreover, the shared decision making model is not universally preferred; numerous situations can be mentioned in which either patient or physician would prefer the paternalistic model [1]. Shared decision making is, however, particularly important when trade-offs between options strongly depend on individual preferences. This includes recommendations within guidelines for which the evidence is scarce or conflicting or for which there is more than one relevant treatment option that different individuals may value differently [2]. This explains why more and more recommendations for shared decision making appear in new guidelines. One of these guidelines is the 2012 version of the Guidelines on the Management of Valvular Heart Disease, by the Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) [3], that reads, on page S9: “Finally, a decision should be reached through the process of shared decision-making, first by a multidisciplinary ‘heart team’ discussion, then by informing the patient thoroughly, and finally by deciding with the patient and family which treatment option is optimal”. Also the new 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease [4] mentions shared decision making several times. Amongst others, this guideline gives the following class I, level of evidence C recommendation: “The choice of valve intervention, that is, repair or replacement, as well as type of prosthetic heart valve, should be a shared decisionmaking process that accounts for the patient’s values and preferences, with full disclosure of the indications for and risks of anticoagulant therapy and the potential need for and risk of reoperation.” Also, in the AHA/ACC guideline, discussion of individual cases in a multidisciplinary ‘heart valve team’ is considered essential. Indeed, extra complexity in shared decision making can arise if multidisciplinary expertise is involved, e.g., cardiology and thoracic sugery in the case of cardiac valve disease. In the current issue of the Netherlands Heart Journal, Korteland and colleagues [5] present a survey among Dutch cardiologists and cardiac surgeons regarding their opinion on decision making in prosthetic aortic valve selection. A total of 117 physicians participated, 54 cardiothoracic surgeons (11 in training) and 63 cardiologists (7 in training), representing 38 % and 6 % of the Dutch cardiothoracic/cardiologist population, respectively. Most respondents agreed that patients should be involved in decision making, with surgeons leaning more toward patient involvement than cardiologists. Most respondents found that patients and doctors should decide together, with cardiologists leaning more toward taking the lead than surgeons. Physicians working in a centre with cardiac surgery were more inclined to decide together with the patient while physicians working in a centre without a cardiac surgery program more often preferred to take the lead in decision making. Shared decision making may not fit all forms of clinical practice, but it seems an appropriate approach in valve intervention, as underscored by the guidelines [3, 4]. It is not sure how much the study results of Korteland and colleagues [5] were influenced by selection bias. Assuming that selection bias is limited, their study suggests that shared decision making in prosthetic aortic valve selection is quite commonly performed in the Netherlands. The difference between the cardiologists’ and surgeons’ responses to the questionnaire remains puzzling. At the same time it is one main raison d'etre for the multidisciplinary heart team as recommended in the guidelines [3, 4].

Antithrombotic therapy in nonvalvular atrial fibrillation: A narrative review

Atrial fibrillation (AF) is an important and potentially modifiable cause of stroke. It has been known since 1989 that oral anticoagulant drugs, such as warfarin, lead to a dramatic decrease in stroke associated with AF. The best risk-benefit ratio is obtained with intensity of oral anticoagulant treatment for an INR of 2-3, even in the elderly. Given the risks of anticoagulant therapy, including bleeding, individual thromboembolic risk must be assessed in patients with AF. In 2009, dabigatran was shown to be a reasonable alternative to vitamin K antagonists, establishing itself as a major alternative to warfarin in AF patients. Rivaroxaban and apixaban have subsequently also been shown to be alternatives to warfarin. When there are contraindications to vitamin K antagonists, antiplatelet agents can produce a therapeutic effect, although much less than oral anticoagulants. Apixaban may be a better alternative to aspirin in this setting. Patients with low-risk atrial fibrillation (no risk factors) have not been the subjects of specific clinical trials. It is unclear what would be the best therapeutic choice for these patients.

Antithrombotic therapy in nonvalvular atrial fibrillation: A narrative review

Atrial fibrillation (AF) is an important and potentially modifiable cause of stroke. It has been known since 1989 that oral anticoagulant drugs, such as warfarin, lead to a dramatic decrease in stroke associated with AF. The best risk-benefit ratio is obtained with intensity of oral anticoagulant treatment for an INR of 2–3, even in the elderly. Given the risks of anticoagulant therapy, including bleeding, individual thromboembolic risk must be assessed in patients with AF. In 2009, dabigatran was shown to be a reasonable alternative to vitamin K antagonists, establishing itself as a major alternative to warfarin in AF patients. Rivaroxaban and apixaban have subsequently also been shown to be alternatives to warfarin. When there are contraindications to vitamin K antagonists, antiplatelet agents can produce a therapeutic effect, although much less than oral anticoagulants. Apixaban may be a better alternative to aspirin in this setting. Patients with low-risk atrial fibrillation (no risk factors) have not been the subjects of specific clinical trials. It is unclear what would be the best therapeutic choice for these patients.

Catheter ablation for atrial fibrillation: Should it be first-line therapy?

Although much has changed in the management of atrial fibrillation (AF) over the past 20 years, pharmacologic therapy still remains the principal means of treatment. h-Adrenergic blockers, calcium-channel blockers, and digoxin are used to slow the ventricular rate during AF. Warfarin and aspirin are used to decrease the stroke risk associated with AF. Class I (eg, propafenone, flecainide, disopyramide) and class III (eg, sotalol, dofetilide, amiodarone) antiarrhythmic drugs are used to decrease the frequency of recurrences of AF. Although these pharmacologic approaches are all relatively effective, there are significant limitations and risks of side effects. Rate control drugs frequently have associated nuisance side effects, such as fatigue, decreased exercise capacity, and sexual dysfunction, and may exacerbate bradyarrhythmias, heart failure, and obstructive lung disease. Pharmacologic approaches for rate control may also be ineffective for controlling rate during AF in up to 25% of patients. Warfarin is substantially more effective than either aspirin alone or the combination of aspirin and clopidogrel for prevention of strokes in patients with AF. Nonetheless, pooled data from prospective trials with warfarin demonstrate only a 65% reduction in stroke risk by intention-to-treat analysis. This lower than expected risk reduction is primarily related to the frequent discontinuation of warfarin because of concerns about bleeding risks and the difficulties maintaining patients in the relatively narrow therapeutic international normalized ratio range of 2 to 3. Based on pooled data from clinical trials, warfarin is associated with a 1% per patient-year risk of major bleeding and a 0.3% per patientyear risk of intracerebral hemorrhage. Accumulated over time; this represents a substantial risk to patients. The risks of anticoagulation therapy are even worse under more typical clinical circumstances (ie, outside of controlled clinical studies), where the risk of major bleeding may be as high as 12%. Perhaps most controversial is the use of class I or III antiarrhythmic drugs for suppression of AF recurrences.

Preoperative haemoglobin and warfarin response

There is a narrow line between the benefits and risks of anticoagulant therapy. Many factors influence a patient’s response to warfarin, and careful monitoring is required to ensure that the therapeutic level of anticoagulation is achieved. The purpose of this retrospective review was to examine the relationship between the postoperative response to warfarin and the preoperative level of haemoglobin. The results showed that lower preoperative levels of haemoglobin are associated with an increased response to warfarin (p = 0.01).

Preoperative haemoglobin and warfarin response

There is a narrow line between the benefits and risks of anticoagulant therapy. Many factors influence a patient's response to warfarin, and careful monitoring is required to ensure that the therapeutic level of anticoagulation is achieved. The purpose of this retrospective review was to examine the relationship between the postoperative response to warfarin and the preoperative level of haemoglobin. The results showed that lower preoperative levels of haemoglobin are associated with an increased response to warfarin (p = 0.01).

Optimal management strategy for use of compression US for deep venous thrombosis in symptomatic patients: A cost-effectiveness analysis

The authors' purpose was to identify the optimal strategy for using compression ultrasonography (US) in patients suspected of having deep venous thrombosis (DVT). The authors developed a decision-analytic model representing the natural history of DVT and the benefits and risks of anticoagulation therapy. They evaluated six initial imaging strategies: (a) unilateral examination of the common femoral and popliteal veins; (b) unilateral examination of the common femoral, popliteal, and femoral veins; (c) bilateral examination of the common femoral and popliteal veins; (d) bilateral examination of the common femoral, popliteal, and femoral veins; (e) complete unilateral examination of the symptomatic leg (including calf veins); and (f) complete bilateral examination of both legs. For 65-year-old men with unilateral symptoms of DVT, the most effective strategy was bilateral examination of the common femoral and popliteal veins with anticoagulation therapy in patients with proximal DVT and follow-up bilateral examination of the common femoral and popliteal veins in patients without an initial diagnosis of DVT with an incremental cost-effectiveness ratio of $39,000 per quality-adjusted life year gained. These results suggest that bilateral examination limited to the common femoral and popliteal veins, with follow-up bilateral examination limited to the common femoral and popliteal veins, was as cost-effective as other well-accepted medical interventions. The results were sensitive to the distribution of clot, diagnostic accuracy of compression US, and probability of bleeding with long-term morbidity.

Syndrome des anticorps antiphospholipides en neurochirurgie pédiatrique: un problème d'hémostase

The case of a 11-year-old boy under anticoagulant therapy for a familial antiphospholipid antibody syndrome (SAAPF), who underwent surgery for a cerebrovascular malformation responsible for an intracerebral haematoma, is reported. Antivitamins K (AVK) were changed for unfractioned heparin (HNF), three days before. Heparin was discontinued two hours prior to surgery to obtain a normal peroperative coagulation. A vascular dural fistula was removed without any haemostatic problem. The neurological status rapidly returned to normal and tomodensitometry at day 1 showed a normal intracranial status. Heparin was readministered at h 16. Thrombocytopenia occurred at day 4 of heparin treatment. The change for a low weight molecular heparinoid, danaparoid (Orgaran), normalized the platelet count. The platelets aggregation tests were negative during thrombopenia. However, the test for antibodies against the PF4-heparin complex with the Elisa technique, was in favour of a heparin induced thrombocytopenia (TIH). In spite of its anecdotic occurrence due to cumulative thrombotic risks from the association of immunologic disorders (TIH and SAAPF), this case report underlines the value but also the risks of anticoagulant therapy in neurosurgery, when patients are at high risk for thrombosis.

Current Clinical Concepts in Perioperative Anticoagulation

Management of patients with significant risks for thromboembolism in the perioperative period requires consideration of both risks of thromboembolism and risks of anticoagulant therapy. Patients who are receiving warfarin therapy because of recent venous thromboembolism, nonvalvular atrial fibrillation, and mechanical heart valves are at increased risk during the interval when the warfarin is discontinued and when the international normalized ratio is at a subtherapeutic level. In patients with an acute venous thromboembolic event within the past month, the use of intravenous heparin appears to be justified both preoperatively and postoperatively. If the venous thromboembolic event was within the past 2 to 3 months, use of intravenous heparin appears justified in the postoperative period. More than 3 months after an acute episode of venous thrombophlebitis, the relatively low risk of recurrence does not appear to justify the risks of complications from intravenous heparin. Patients with increased risks of arterial embolism, specifically those with nonvalvular atrial fibrillation and mechanical heart valves, are generally not at sufficient risk of arterial embolism to justify use of intravenous heparin during the perioperative subtherapeutic international normalized ratio interval when warfarin is withheld. A potential increased risk of recurrent arterial embolism when the preceding event was within a month suggests that elective surgery should be deferred beyond a month whenever possible in such patients. The use of fixed-dose, subcutaneous low molecular weight heparin has been observed to have advantages over use of unfractionated intravenous heparin both in terms of safety and efficiency. Further refinements in management of patients with significant risks of thromboembolism may occur with increased experience with low molecular weight heparin.

Thromboembolism and Antithrombotic Therapy in Congestive Heart Failure

The incidence of thromboembolic events in unselected patients with class II-III congestive heart failure is 1.6-3.5% per year. Marked limitation of exercise capacity and the presence of echocardiographic left ventricular thrombus appear to be associated with an increased risk of thromboembolism. Several studies have reported that anticoagulant therapy does not eliminate the occurrence of thromboembolism. Because the benefit and risks of anticoagulant therapy in patients with congestive heart failure have not been examined in controlled studies, it is difficult to make well-founded recommendations.