Antifactor Xa Activity for the Management of Anticoagulation during Cardiac Surgery

Background In patients with autoimmune diseases associated with antiphospholipid antibodies, precise management of anticoagulation during extracorporeal circulation (ECC) is complicated. It was the aim of the present study to determine whether antifactor Xa (aXa) activity is useful in guiding heparin therapy during ECC. Methods In 15 patients undergoing cardiac surgery, anticoagulation with unfractionated heparin (UFH) and its reversal with protamine were guided using activated clotting time (ACT) (>400 second during ECC; ≤100 second for UFH reversal). For each ACT, the corresponding aXa activity levels were measured. Results A total of 144 blood samples were obtained. ACT and aXa activity were significantly correlated (r = 0.771, p< 0.0001, Spearman rank-order correlation). Using receiver operating characteristic curve (ROC) analyses, the cutoffvalues for aXa activity were 1.14 IU/mL (area under the ROC curve [AUC]: 0.89; inaccuracy rate: 9.4%) to predict ACT > 400 seconds and 0.55 IU/mL (AUC: 0.85; inaccuracy rate: 13.3%) for ACT ≤ 100 seconds. Conclusion AXa activity is strongly correlated with ACT, and therefore may be feasible for managing anticoagulation with UFH during ECC.

Bivalirudin for Alternative Anticoagulation in Extracorporeal Membrane Oxygenation: A Systematic Review.

BACKGROUND Extracorporeal membrane oxygenation (ECMO) offers therapeutic options in refractory respiratory and/or cardiac failure. Systemic anticoagulation with heparin is routinely administered. However, in patients with heparin-induced thrombocytopenia or heparin resistance, the direct thrombin inhibitor bivalirudin is a valid option and has been increasingly used for ECMO anticoagulation. We aimed at evaluating its safety and its optimal dosing for ECMO. METHODS Systematic web-based literature search of PubMed and EMBASE performed via National Health Service Library Evidence and manually, updated until January 30, 2016. RESULTS The search revealed 8 publications relevant to the topic (5 case reports). In total, 58 patients (24 pediatrics) were reported (18 received heparin as control groups). Bivalirudin was used with or without loading dose, followed by infusion at different ranges (lowest 0.1-0.2 mg/kg/h without loading dose; highest 0.5 mg/kg/h after loading dose). The strategies for monitoring anticoagulation and optimal targets were dissimilar (activated partial thromboplastin time 45-60 seconds to 42-88 seconds; activated clotting time 180-200 seconds to 200-220 seconds; thromboelastography in 1 study). CONCLUSION Bivalirudin loading dose was not always used; infusion range and anticoagulation targets were different. In this systematic review, we discuss the reasons for this variability. Larger studies are needed to establish the optimal approach with the use of bivalirudin for ECMO.

The effect of anticoagulation on the restoration of range of motion after total knee arthroplasty: Enoxaparin versus aspirin

Anticoagulation used for thromboembolic prophylaxis following total knee arthroplasty (TKA) could interfere with movement. This study compares the effect of 2 anticoagulants, enoxaparin and aspirin, on restoration of range of motion (ROM) after TKA. Two groups of 75 consecutive patients, matched for age, arthritic severity, and preoperative ROM, underwent TKA. Flexion and extension milestone measures were recorded daily. Results show a highly statistically significant difference (P

Development and trialling of a behavioural intervention for patients with atrial fibrillation initiating oral anticoagulation:the 'treat' study

Purpose: Atrial fibrillation (AF) is the most common heart arrhythmia and is associated with an increased risk of stroke. Stroke risk is commonly treated with oral anticoagulation (OAC) with a narrow therapeutic range (INR 2.0 to 3.0); which is poorly controlled in practice. Barriers to adherence include poor knowledge, and inaccurate perceptions surrounding illness and medications. Trial registration: ISRCTN93952605. Systematic review: Seven trials of educational, self-monitoring and decision aid interventions were included in a systematic review. Pooled analysis suggested education OR, 95% CI 7.89 (5.54-10.24) and self monitoring OR (95% CI) 5.47(2.55-8.39) significantly improve TTR; whereas decision aids are no more effective in reducing decision conflict than usual care, OR (95% CI) -0.10 (-0.17 to -0.02). Intervention development: The intervention was theoretically-driven (utilising the common sense and beliefs about medication models) and developed with expert patient feedback. Described using behavioural change techniques, the one-off group session included an educational booklet, ‘expert-patient’ focussed DVD, and worksheet. Methods: Ninety seven warfarin-naïve AF patients were randomised to receive the intervention (n=43), or usual care (n=54). The primary endpoint was time within therapeutic range (TTR), secondary endpoints included knowledge, quality of life (AF-QoL-18), beliefs about medication (BMQ), illness perceptions (IPQ-B), and anxiety and depression (HADS). Results: Intervention group had significantly higher TTR than usual care (78.5% vs. 66.7%; p=0.01). Knowledge changed significantly across time (F (3, 47) = 6.4; p<0.01), but not between groups (F (1, 47) = 3.3; p = 0.07). At six months knowledge predicted TTR (r=0.245; p=0.04). Illness concern negatively correlated with TTR (r= - 0.199; p=0.05). General Harm scores at one month predicted TTR (F (1, 72) = 4.08; p=0.048). There were significant differences in emotional representations (F (3, 49) = 3.3 (3, 49); p= 0.03), anxiety (F (3, 46) = 25.2; p<0.01) and depression (F (3, 46) = 37.7; p<0.01) across time. Conclusion: A theory-driven educational intervention can improve TTR in AF patients and potentially reduce the risk of adverse clinical outcomes. Improving education provision for AF patients is essential to ensure efficacious treatment.

Patients’ and physicians’ experiences of atrial fibrillation and anticoagulation therapy:a qualitative journey

Background: Oral anticoagulation (OAC) reduces stroke risk in patients with atrial fibrillation (AF) however it is often underutilized and sometimes refused by patients. This programme of work included a meta-synthesis and two inter-linking studies aiming to explore patients’ and physicians’ experiences of AF and OAC. Methods: A meta-synthesis of qualitative evidence was conducted which informed the empirical work. Semi-structured individual interviews were utilised. Study 1: Three AF patient sub-groups were interviewed; accepted (n=4), refused (n=4), or discontinued (n=3) warfarin. Study 2: Four physician sub-groups (n=4 each group) prescribing OAC to AF patients were interviewed: consultant cardiologists, consultant general physicians, general practitioners and cardiology registrars. Data was analysed using interpretative phenomenological analysis. Results: Study 1: Three over-arching themes comprised patients’ experiences: (1) the initial consultation, (2) life after the consultation, and (3) patients’ reflections. Patients commented on the relief and reassurance experienced during the consultation but they perceived the decision making process mostly led by the physician. Lack of education and take-home materials distributed during the initial consultation was highlighted. Patients who had experienced stroke themselves or were caregivers, were more receptive to education aimed towards stroke risk reduction rather than bleeding risk. Warfarin monitoring was challenging for patients, however some patients perceived it as beneficial as it served to enhance patient-physician relationship. Study 2: Two over-arching themes emerged from physicians’ experiences: (1) communicating information and (2) challenges with OAC prescription for AF. Physicians’ approach to the consultation style shifted through a continuum of compliance-adherence-concordance during the consultation. They aimed for concordance, however challenges such as time and the perceived patient trust in them as the expert, led to physicians adopting a paternalistic approach. Physicians also pointed out challenges associated with guideline adherence and the need to adopt a multi-disciplinary approach, where other health professionals could provide on-going education. Conclusion: This programme of work has illustrated the benefit of taking an in depth phenomenological approach to understanding the lived experience of the physician-patient consultation. Together with the meta-synthesis, this work has strengthened the evidence base and demonstrated that there is a need to target patients' and physicians' ability to communicate with each other in a comprehensible way.

Educational intervention improves anticoagulation control in atrial fibrillation patients:the TREAT randomised trial

Background: Stroke prevention in atrial fibrillation (AF), most commonly with warfarin, requires maintenance of a narrow therapeutic target (INR 2.0 to 3.0) and is often poorly controlled in practice. Poor patient-understanding surrounding AF and its’ treatment may contribute to patient’s willingness to adhere to recommendations. Method: A theory-driven intervention, developed using patient interviews and focus groups, consisting of a one-off group session (1-6 patients) utilising an ‘expert-patient’ focussed DVD, educational booklet, self-monitoring diary and worksheet, was compared in a randomised controlled trial (ISRCTN93952605) against usual care, with patient postal follow-ups at 1, 2, 6, and 12-months. Ninety-seven warfarin-naïve AF patients were randomised to intervention (n=46, mean age (SD) 72.0 (8.2), 67.4% men), or usual care (n=51, mean age (SD) 73.7 (8.1), 62.7% men), stratified by age, sex, and recruitment centre. Primary endpoint was time within therapeutic range (TTR); secondary endpoints included knowledge, quality of life, anxiety/depression, beliefs about medication, and illness perceptions. Main findings: Intervention patients had significantly higher TTR than usual care at 6-months (76.2% vs. 71.3%; p=0.035); at 12-months these differences were not significant (76.0% vs. 70.0%; p=0.44). Knowledge increased significantly across time (F (3, 47) = 6.4; p<0.01), but there were no differences between groups (F (1, 47) = 3.3; p = 0.07). At 6-months, knowledge scores predicted TTR (r=0.245; p=0.04). Patients’ scores on subscales representing their perception of the general harm and overuse of medication, as well as the perceived necessity of their AF specific medications predicted TTR at 6- and 12-months. Conclusions: A theory-driven educational intervention significantly improves TTR in AF patients initiating warfarin during the first 6-months. Adverse clinical outcomes may potentially be reduced by improving patients’ understanding of the necessity of warfarin and reducing their perception of treatment harm. Improving education provision for AF patients is essential to ensure efficacious and safe treatment.

Heparin elevates circulating soluble fms-like tyrosine kinase-1 immunoreactivity in pregnant women receiving anticoagulation therapy

Background—Alterations in circulating levels of pro- and antiangiogenic factors have been associated with adverse pregnancy outcomes. Heparin is routinely administered to pregnant women, but without clear knowledge of its impact on these factors. Methods and Results—We conducted a longitudinal study of 42 pregnant women. Twenty-one women received prophylactic heparin anticoagulation, and 21 healthy pregnant women served as controls. Compared with gestational age-matched controls, heparin treatment was associated with increased circulating levels of soluble fms-like tyrosine kinase-1 (sFlt-1) in the third trimester (P<0.05), in the absence of preeclampsia, placental abruption, or fetal growth restriction. Heparin had no effect on circulating levels of vascular endothelial growth factor, placenta growth factor, or soluble endoglin as assessed by ELISA. In vitro, low-molecular weight and unfractionated heparins stimulated sFlt-1 release from placental villous explants, in a dose- and time-dependent manner. This effect was not due to placental apoptosis, necrosis, alteration in protein secretion, or increased transcription. Western blot analysis demonstrated that heparin induced shedding of the N-terminus of Flt-1 both in vivo and in vitro as indicated by a predominant band of 100–112 kDa. By using an in vitro angiogenesis assay, we demonstrated that serum of heparin-treated cases inhibited both basal and vascular endothelial growth factor-induced capillary-like tube formation. Conclusions—Heparin likely increases the maternal sFlt-1 through shedding of the extracellular domain of Flt-1 receptor. Our results imply that upregulation of circulating sFlt-1 immunoreactivity in pregnancy is not always associated with adverse outcomes, and that heparin's protective effects, if any, cannot be explained by promotion of angiogenesis.

Patients' and physicians' experiences of atrial fibrillation consultations and anticoagulation decision-making:a multi-perspective IPA design

OBJECTIVE: To explore patients' and physicians' experiences of atrial fibrillation consultations and oral anticoagulation decision-making. DESIGN: Multi-perspective interpretative phenomenological analyses. METHODS: Participants included small homogeneous subgroups: AF patients who accepted (n=4), refused (n=4), or discontinued (n=3) warfarin, and four physician subgroups (n=4 each group): consultant cardiologists, consultant general physicians, general practitioners and cardiology registrars. Semi-structured interviews were conducted. Transcripts were analysed using multi-perspective IPA analyses to attend to individuals within subgroups and making comparisons within and between groups. RESULTS: Three themes represented patients' experiences: Positioning within the physician-patient dyad, Health-life balance, and Drug myths and fear of stroke. Physicians' accounts generated three themes: Mechanised metaphors and probabilities, Navigating toward the 'right' decision, and Negotiating systemic factors. CONCLUSIONS: This multi-perspective IPA design facilitated an understanding of the diagnostic consultation and treatment decision-making which foregrounded patients' and physicians' experiences. We drew on Habermas' theory of communicative action to recommend broadening the content within consultations and shifting the focus to patients' life contexts. Interventions including specialist multidisciplinary teams, flexible management in primary care, and multifaceted interventions for information provision may enable the creation of an environment that supports genuine patient involvement and participatory decision-making.

Psychological influence of the media on patients commencing oral anticoagulation in atrial fibrillation:a qualitative analysis

Background: Oral anticoagulation (OAC) reduces stroke risk in patients with atrial fibrillation (AF); however it is still underutilized and sometimes refused by patients. Two inter-related studies were undertaken to understand the experiences and what influences this un- derutilisation of warfarin treatment in AF patients. These studies explored physician and patient experiences of AF and OAC treatment. The paper focuses on specific sub-themes from the study that explored patients’ experiences will be discussed. Aim: The study in question aimed to explore the experiences which influence patients’ decisions to accept, decline or discontinue OAC. Methods: Semi-structured individual interviews with patients were con- ducted. Three sub-groups of patients (n = 11) diagnosed with AF were interviewed; those who accepted, refused, and who discontinued war- farin. Interpretative phenomenological analysis (IPA) was used to examine the data. IPA is a qualitative method that focuses on how participants make sense of an experiences phenomenon Results: Three over-arching themes comprised patients’ experiences: (i)the initial consultation, (ii) life after the consultation, and (iii) patients’reflections. In the last theme, patients reflected on their perceptions ofaspirin and warfarin. Aspirin was perceived as a natural wonder-drugwhile warfarin was perceived as a dangerous drug usually given to peo-ple at the end of their life. Interestingly they perceive both drugs as‘old’. However, for aspirin it had a positive association, old meaningtried and tested. While for warfarin, old meant ‘has been around fortoo long’.Conclusion: Media had an important role in how patients’ perceptionsof these two drugs were influenced. Literature shows that framingtechniques, i.e. using certain words or phrases such as ‘rat poison’, areprocesses adopted by media to alter medical knowledge into lay per-son’s language. Patients in turn form negative cognitive schemas,between the word ‘poison’ and warfarin, leading to the negative per-ception of warfarin which could influence non-adherence to treatment.This qualitative research highlighted the potential influences of themedia on AF patient perceptions commencing OAC treatment. Theassociation between media stimuli and patient perceptions on OACshould be further explored. The influential power of lay-media couldalso be instrumental in disseminating appropriate educational materialto the public

Safety and Use of Anticoagulation After Aortic Valve Replacement With Bioprostheses: A Meta-Analysis.

BACKGROUND: The American College of Cardiology guidelines recommend 3 months of anticoagulation after replacement of the aortic valve with a bioprosthesis. However, there remains great variability in the current clinical practice and conflicting results from clinical studies. To assist clinical decision making, we pooled the existing evidence to assess whether anticoagulation in the setting of a new bioprosthesis was associated with improved outcomes or greater risk of bleeding. METHODS AND RESULTS: We searched the PubMed database from the inception of these databases until April 2015 to identify original studies (observational studies or clinical trials) that assessed anticoagulation with warfarin in comparison with either aspirin or no antiplatelet or anticoagulant therapy. We included the studies if their outcomes included thromboembolism or stroke/transient ischemic attacks and bleeding events. Quality assessment was performed in accordance with the Newland Ottawa Scale, and random effects analysis was used to pool the data from the available studies. I(2) testing was done to assess the heterogeneity of the included studies. After screening through 170 articles, a total of 13 studies (cases=6431; controls=18210) were included in the final analyses. The use of warfarin was associated with a significantly increased risk of overall bleeding (odds ratio, 1.96; 95% confidence interval, 1.25-3.08; P<0.0001) or bleeding risk at 3 months (odds ratio, 1.92; 95% confidence interval, 1.10-3.34; P<0.0001) compared with aspirin or placebo. With regard to composite primary outcome variables (risk of venous thromboembolism, stroke, or transient ischemic attack) at 3 months, no significant difference was seen with warfarin (odds ratio, 1.13; 95% confidence interval, 0.82-1.56; P=0.67). Moreover, anticoagulation was also not shown to improve outcomes at time interval >3 months (odds ratio, 1.12; 95% confidence interval, 0.80-1.58; P=0.79). CONCLUSIONS: Contrary to the current guidelines, a meta-analysis of previous studies suggests that anticoagulation in the setting of an aortic bioprosthesis significantly increases bleeding risk without a favorable effect on thromboembolic events. Larger, randomized controlled studies should be performed to further guide this clinical practice.