Anticoagulation Regimen Research Articles

Outcomes of aortic root replacement in patients with Marfan syndrome: the role of valve-sparing and valve-replacing approaches.

Marfan syndrome (MFS) is a heritable thoracic aortic disease with pervasive cardiovascular effects, including commonly, a dilated aortic root. Traditionally, the root is replaced using a mechanical composite valve graft (CVG); however, this valve-replacing (VR) approach necessitates a lifelong regimen of anticoagulation with a potential for late bleeding complications. In time, valve-sparing (VS) approaches were developed. Today, several options for aortic root replacement (ARR) exist; each has advantages and disadvantages that helps inform choice. The Aortic Valve Operative Outcomes in Marfan Patients (AVOMP) is a multi-center international registry to analyze clinical outcomes of ARR in MFS patients using either VR or VS techniques to better elucidate choice. We summarize outcomes of AVOMP and present our own experience. We performed 223 consecutive elective ARR [1991-2023] in patients with MFS; 15 such repairs were included in AVOMP. Repairs included 113 (51%) using a mechanical CVG, 62 (28%) using a VS approach, and 48 (22%) using a bioprosthetic root. Many patients underwent aortic arch repair (30% to 54% by type). The median patient age was 38 [29-52] years. In comparing VS and VR groups, patients were similar in age and rates of major comorbidities and symptoms. Patients with VR repair had a more complex aortic history. The rate of redo sternotomy was 24% (n=54). Operative death was uncommon [4% overall (10/223); ranging from 2% to 8% by type], and stroke was rare [1/223 (<1%)]. Late survival and reoperation differed by operative approach; survival was improved in patients who underwent VS repair. We found that repair in patients with MFS undergoing ARR resulted in low operative risk. Our late results were similar to those of AVOMP in that patients undergoing VS repair tended to experience greater rates of valvular-structural deterioration, although this did not appear to impact survival.

Effect of combination of prophylactic or therapeutic anticoagulation with aspirin on the outcomes of hospitalized COVID-19 patients: An observational retrospective study.

Regimens for managing thromboembolic complications of COVID-19 are still not very well established. The present study compares the clinical characteristics and outcomes of patients hospitalized with COVID-19 receiving different anticoagulation regimens with and without aspirin. This is a retrospective observational study of 491 patients hospitalized for COVID-19 from August 2020 to April 2021. Data regarding clinical characteristics, laboratory findings, and outcomes of patients receiving different anticoagulation with and without aspirin regimens was collected, according to which 5 patient groups were defined: received no anticoagulation (NAA), prophylactic anticoagulation with (PA) or without aspirin (PAA) and therapeutic anticoagulation with (TA) or without aspirin (TAA). The average age was highest in the TAA group. Desaturation was highest in the TA and TAA groups. Diabetes, hypertension, dyslipidemia and coronary artery disease were the most prevalent in aspirin groups (PAA and TAA) as was heart failure in the TA and TAA groups and cancer in the TA and PAA groups. Elevated troponin was observed in the PAA and TAA groups. TA and TAA patients received oxygen therapy, needed ICU admission overall, and required invasive ventilation and vasopressors the most. Prophylactic anticoagulation groups (PA and PAA) had the highest patient survival rates. Patients with severe COVID-19 infections were more likely to receive higher, therapeutic, anticoagulation doses. Aspirin was given to patients with preexisting comorbidities, but it had no statistically significant impact on the outcomes of the different groups. Groups receiving prophylactic anticoagulation had the best survival outcomes.

Contemporary early left ventricular thrombus resolution by echocardiography: insight from a longitudinal multicenter registry

Abstract Funding Acknowledgements Type of funding sources: None. Background Multicenter longitudinal data are lacking regarding the incidence and the time needed for total left ventricular thrombus (LVT) regression obtained with contemporary antithrombotic regimens diagnosed with modern echocardiographic technology. Purpose To quantify the effect of antithrombotic therapy on LVT evolution using sequential up-to-date echocardiography in a large cohort of patients with LVT. Methods Ten centers were involved in this observational prospective multicenter study. LVT was defined as an echo-dense mass adjacent to a hypokinetic or akinetic myocardial segment. To be distinguishable from the underlying myocardium, a clear thrombus–blood interface was required and the LVT had to be visible on at least 2 views during the cardiac cycle. Initial follow-up echocardiograph was scheduled at 14±7 days (T0) and 42±7 days (T1). The early resolution was defined when LVT was no longer detected at T1. The use of different anticoagulant regimens and ultrasound contrast was left at the discretion of attending physicians, according to good clinical practice. Results From October 2020 to November 2022, 99 patients with LVT (mean age 66 ± 11 years, 80% men) were identified with echocardiography, in 53% ultrasound contrast was used. Early resolution of LVT was observed in 42%. Echocardiographic characteristics by early resolution of LVT are shown in Table. The independent correlates of early LVT regression were smaller baseline LVT area, higher LVEF, and mobile LVT (p&amp;lt;0.05). Conclusions In this large and well-characterized present-day cohort of patients with LVT, early regression by echocardiography was achieved in less than half of the patients and was mostly related to the size of the LVT and heart function rather than treatment despite a high proportion of antithrombotic therapy. The next step will be to assess the impact of LVT persistence on subsequent clinical outcomes.

Hypoattenuated Leaflet Thickening After Implantation of the ACURATE neo or the ACURATE neo2 Transcatheter Heart Valve

Subclinical leaflet thrombosis, identified as hypoattenuated leaflet thickening (HALT) on cardiac computed tomography scan, has been observed after transcatheter aortic valve replacement (TAVR). However, data on HALT after the implant of the supra-annular ACURATE neo/neo2 prosthesis are limited. This study aimed to determine the prevalence and risk factors for the development of HALT after TAVR with the ACURATE neo/neo2. A total of 50 patients who received the ACURATE neo/neo2 prosthesis were prospectively enrolled. Patients underwent a contrast-enhanced multidetector row cardiac computed tomography scan at before, after, and 6months after TAVR. At the 6-month follow-up, HALT was detected in 16% (8 of 50 patients). These patients had a lower implant depth of the transcatheter heart valve (8 ± 2mm vs 5 ± 2mm, p=0.001), less calcified native valve leaflets, a better expansion of the frame at the level of the left ventricular outflow tract, and were less often hypertensive. Thrombosis of the sinus of Valsalva occurred in 18% (9/50). There was no difference in the anticoagulation regimen between patients with and without thrombotic findings. In conclusion, HALT was present in 16% of patients at 6months follow-up, patients presenting with HALT had a lower implant depth of the transcatheter heart valve, and HALT was detected in patients on oral anticoagulation therapy.

Impact of oral anticoagulant regimens on occurrence of contrast-induced nephropathy in patients undergoing coronary angioplasty.

Ricottini, Elisabetta; Giannone, Sara; Melfi, Rosetta; Nusca, Annunziata; Mangiacapra, Fabio; Gallo, Paolo; Cocco, Nino; Rinaldi, Raffaele; Ussia, Gian Paolo; Grigioni, Francesco Author Information

Omitting transesophageal echocardiography before catheter ablation of atrial fibrillation or left sided atrial tachycardia in patients on oral anticoagulation

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Catheter ablation (CA) is accepted as a safe and effective therapy for atrial Fibrillation AF and left sided atrial tachycardias (AT) and is a well-established standard of care. However, the procedure can lead to life-threatening complications, including thromboembolic cerebrovascular events (CVE). Transesophageal echocardiography (TOE) is the gold standard for screening for left atrial appendage thrombus (LAAT) and is performed in many cases prior to CA of AF. However, the guidelines are limited on the precise role of LA imaging for thrombus detection prior to CA. Purpose The aim of our retrospective analysis was to evaluate the safety of individualized TOE approach for patient undergoing CA of AF or left sided AT in the two participating centers. Methods Patients, undergone AF or left sided AT ablation between August 2018 and October 2022 at two centers were enrolled. Patients were scheduled to TOE when one of the following criteria was met: 1) prior history of either thromboembolic stroke or 2) LAAT, 3) inappropriate anticoagulation (OAK) regimen in 4 weeks prior to CA. Otherwise, no TOE prior to CA was performed. (Figure 1). TOE and CA outcomes were retrospectively analyzed. CVE incidence from the procedure onset to 24 hours post-procedure was evaluated. Results A total of 1156 Patients were analyzed. The median age of study population was 70 (IQR: 62-76) years. 675 patients (58.4%) were male, 555(48.1%) had a persistent AF/AT and 358 (31%) had already left atrial CA in prior history. The CHA2DS2-VASc score was ≥ 2 in 939 (81.2%) patients. 505 patients (43.7%) were on apixaban, 359(31.0%) on rivaroxaban, 22 (1,9%) on dabigatran, 103 (8.9%) on edoxaban, 94(8.13%) on VKA, 73(6.3%) had no OAK prior to ablation (6 patients due to previous LAA occluder implantation, in 1 patient due to LAA resection). The median left ventricular ejection fraction was 59% (IQR: 50-60%), median left atrial volume index was 43.6 (IQR: 28.8-55) ml/m2.TOE was performed in 261 (22.6%) of patients, in 93 due to stroke history, in 24 due to LAAT history, in 161 due to inappropriate OAK. No LAA Thrombi were detected. Total 4 out of 1156 (0.35%) experienced CVE (Table 1). In 2 of these cases TOE was performed prior to CA, and LAA thrombi were ruled out. In another 2 patients in heart computer tomography immediately after stroke LAAT were excluded. Even not statistically significant, the higher rate of the CVE among the patients with TOE performed (2 out of 261 patients, 0.76%) emphasizes the higher baseline risk of thromboembolic events in this category of patients as opposed to the patients with low stroke risk where TOE was omitted (2 out of 895 patients, 0.22%, p=0.22). Conclusions Individualized selective approach to TOE prior to CA of AF or left sided AT showed to be safe. The stroke incidence (0.35%) in this approach was not higher, than in large cohort studies. In patients with uninterrupted OAK and low stroke risk TOE prior to CA could be omitted.

P467 CHALLENGING MANAGEMENT OF ORAL ANTICOAGULANT THERAPY IN A OBESE PATIENT WITH DILATED CARDIOMYOPATHY, ATRIAL FIBRILLATION AND ICD LEAD THROMBUS

Abstract Obesity is a worldwide epidemic condition at high risk for AF development; nevertheless, obese patients are underrepresented in RCTs of anticoagulant agents. Robust evidence assessing efficacy of DOACs in these patients is lacking and, to date, major Associations do not recommend DOACs in patients &amp;gt; 120 Kg (BMI&amp;gt;40 Kg/m2). The use of implantable cardiac devices has substantially increased in recent years; among potential complications are sterile intracardiac clots on the leads, typically discovered as incidental echocardiographic findings. 46 ys old male patient, III degree obesity (160 Kg,BMI 51 Kg/m2), ex–smoker. In 2012, acute heart failure and diagnosis of non–ischemic dilated cardiomyopathy (EF 20%). During the follow–up by a tertiary Center, in 2021 he was implanted with single–chamber ICD in primary prevention. At presentation, HFrEF pharmacological therapy was optimal (ARNI,SLGT2i,MRA,B–blocker). He came to the ED complaining of weakness; ECG showed atrial fibrillation, mean ventricular rate 160 bpm. CHA2DS2–VASc was 1. Anticoagulation with subcutaneous enoxaparin 10000UI twice daily was started. He was admitted to the cardiology ward and remained hemodynamically stable, with persistence of AF. Transesophageal echocardiography excluded thrombus in the left atrial appendage; unexpectedly, a filamentous, floating formation of about 30mm on the atrial side of the ICD lead was observed, compatible with a thrombotic formation, since the patient, afebrile, didn’t show any suggestive sign of endocarditis nor past history of infection; blood cultures, CRP and Procalcitonin were negative. In the absence of any shunt at the level of interatrial septum, it was felt safe to proceed to electrical cardioversion, able to restore sinus rhythm with a single 250J biphasic synchronized shock. Oral anticoagulation with warfarin was started, since no DOAC was considered adequate for effective anticoagulation. The following in hospital course and post–discharge weeks were uneventful, despite unstable INR values. Follow–up is ongoing; the patient has not yet repeated imaging to check for mass resolution. Stroke prevention in severely obese patients with AF is challenging and points toward warfarin use, as the evidence of DOACs efficacy is sparse. In our case, anticoagulant choice was also motivated by concomitant presence of a lead thrombus, a scenario in which optimal management and anticoagulation regimen are not clearly established yet.

P243 EXTRACORPOREAL CONTINUOUS VENO–VENOUS ULTRAFILTRATION IN PATIENTS WITH ACUTE HEART FAILURE REFRACTORY TO DIURETIC THERAPY: A SINGLE–CENTER PILOT EXPERIENCE

Abstract Introduction Congestive Acute Heart Failure (C–AHF) is characterized by extracellular fluid overload. Extensive use of loop diuretics may induce worsening renal function, electrolyte imbalance, symptomatic hypotension and diuretic resistance. Extracorporeal veno–venous ultrafiltration (UF) may represent a useful adjunctive therapy. Despite a few randomized clinical trials have been carried out, the results are controversial; aim of this study is to describe our pilot experience using UF. Methods We enrolled consecutive patients with C–AHF refractory to diuretic therapy treated with UF from January to December 2022; patients affected by concomitant acute coronary syndrome were excluded. UF was delivered using a modern device specifically designed for fluid removal in C–AHF patients through slow continuous UF (Fig.1). According to our protocol, the initial UF rate was based on baseline systolic arterial pressure (250cc/h if&amp;gt;120mmHg, 100–120cc/h if 100–120mmHg and &amp;lt;100cc/h if&amp;lt;100mmHg; contra–indicated if&amp;lt;90mmHg). Laboratories values, urinary output and fluid balance were monitored at baseline, after 6 hours (T6) and when UF was stopped (T0). Variables are expressed as medians with 25p–75p. Results Seven patients were enrolled in the study (5M;2F); in each a femoral central venous catheter (20cm/14G) was placed to perform UF. A standard anticoagulation regimen based on UFH bolus + infusion was adopted aiming to an ACT of 180–220. Median age and LVEF were respectively 40[20–50] and 79[73–85]; 3 patients were diabetics, 2 smokers and 4 hypertensive. Median rate of hospitalization in the previous 12 months was 1 [0–2]; domiciliary dosage of furosemide was 75mg [50–125]. Baseline, T6h and T0 creatinine values were respectively 1.2 [1.1–2], 1.3 [1.1–1.8] and 1.4 [1.1–1.9]. Heart rate and blood pressure were stable during the treatment. UF parameters in the patients of the study are summarized in Tab.1; congestion was resolved or improved in 6/7 patients, no severe complication (bleeding, AKI, death) occurred while 1 premature filter clot is reported. Conclusions Our initial experience with UF is promising. Modern heart failure specific devices appear safe, easy to use and require only minimal training. Compared to extensive i.v. diuretic use, predictable fluid removal through UF may be beneficial as it is characterized by higher excretion of sodium, limited neuro–hormonal activation, enhanced spontaneous diuresis and restoration of diuretic response.

Pregnancy outcomes in women with a mitral valve prosthesis: A systematic review and meta-analysis

ObjectivesTo evaluate the ongoing debate concerning the choice of valve prosthesis for women requiring mitral valve replacement (MVR) and who wish to conceive. Bioprostheses are associated with risk of early structural valve deterioration. Mechanical prostheses require lifelong anticoagulation and carry maternal and fetal risks. Also, the optimal anticoagulation regimen during pregnancy after MVR remains unclear. MethodsA systematic review and meta-analysis was conducted of studies reporting on pregnancy after MVR. Valve- and anticoagulation-related maternal and fetal risks during pregnancy and 30 days’ postpartum were analyzed. ResultsFifteen studies reporting 722 pregnancies were included. In total, 87.2% of pregnant women had a mechanical prosthesis and 12.5% a bioprosthesis. Maternal mortality risk was 1.33% (95% confidence interval [CI], 0.69-2.56), any hemorrhage risk 6.90% (95% CI, 3.70-12.88). Valve thrombosis risk was 4.71% (95% CI, 3.06-7.26) in patients with mechanical prostheses. 3.23% (95% CI, 1.34-7.75) of the patients with bioprostheses experienced early structural valve deterioration. Of these, the mortality was 40%. Pregnancy loss risk was 29.29% (95% CI, 19.74-43.47) with mechanical prostheses versus 13.50% (95% CI, 4.31-42.30) for bioprostheses. Switching to heparin during the first trimester demonstrated a bleeding risk of 7.78% (95% CI, 3.71-16.31) versus 4.08% (95% CI, 1.17-14.28) for women on oral anticoagulants throughout pregnancy and a valve thrombosis risk of 6.99% (95% CI, 2.08-23.51) versus 2.89% (95% CI, 1.40-5.94). Administration of anticoagulant dosages greater than 5 mg resulted in a risk of fetal adverse events of 74.24% (95% CI, 56.11-98.23) versus 8.85% (95% CI, 2.70-28.99) in ≤5 mg. ConclusionsA bioprosthesis seems the best option for women of childbearing age who are interested in future pregnancy after MVR. If mechanical valve replacement is preferred, the favorable anticoagulation regimen is continuous low-dose oral anticoagulants. Shared decision-making remains priority when choosing a prosthetic valve for young women.

Updates in the Incidence, Pathogenesis, and Management of Cancer and Venous Thromboembolism.

Patients with cancer are at higher risk of developing venous thromboembolism (VTE) compared with the general population. This elevated risk is due to several risk factors and multiple, overlapping thrombotic and hemostatic pathophysiological pathways that are specific to this patient population. Hence, the management of cancer-associated VTE can be challenging for clinicians. Patients with cancer-associated VTE are at higher risk of both recurrent events despite anticoagulation and bleeding complications due to the anticoagulant regimens. Direct oral anticoagulants have recently been shown to be effective, safe, and more convenient than parenteral low-molecular-weight heparin for the management of cancer-associated VTE. Despite these recent advances in anticoagulant therapy, many unmet needs remain in these patients (increased risk of bleeding with specific cancer types, drug-to-drug interactions, liver dysfunction). Factor XI inhibitors are currently being assessed for the management of cancer-associated VTE and may help clinicians address these important knowledge gaps.

Head and neck venous thrombosis secondary to pediatric otolaryngologic infection.

Head and neck venous thrombosis is a rare but potentially devastating complication of childhood otolaryngologic infections. This study examines the presentation and management of this condition. A retrospective chart review was performed on all pediatric patients with otolaryngologic infections complicated by cranial and cervical venous thrombosis at a tertiary children's hospital from 2007 to 2018. Patient demographics, presentation, site of infection, thrombosis location, implicated pathogen, length of hospital stay, need for surgery, and anticoagulant regimen were assessed. This study included 33 patients (mean age, 7.5 years; age range, 0.8-17 years; 19 [58%] male). The most common infection source was otologic (n=20), followed by ophthalmic and sinonasal pathology (n=9), and neck infections (n=4). The most common site of thrombosis secondary to ear pathology was the sigmoid sinus. The ophthalmic veins were the most common site of thrombosis for ophthalmic/sinonasal infections. Nine CN VI palsies, one CN VII palsy, and one CN III palsy were observed. Twenty-six subjects (79%) required surgical intervention. All those who experienced a nerve palsy required surgery. Length of hospitalization significantly differed with the stay for a neck infection complicated by thrombosis longer compared to otologic and sinonasal infections (F[2,30]=7.08, p=0.003). Length of hospital stay was significantly correlated with admission temperature (r=0.506, p=0.003) and CRP (r=0.400, p=0.03) but not WBC (r=0.181, p=0.31). Culture growth predominantly isolated a single causative organism rather than polymicrobial involvement. Forty-eight species were identified, most (n=41/48, 85%) being Gram-positive bacteria. Alpha-hemolytic Streptococcus was the most common isolate from children with vessel thrombosis secondary to ear infections, with Streptococcus pyogenes predominant in sinonasal infections and Staphylococcus aureus the most common in neck abscesses. There was significant variability in anticoagulation management within the patient population, but no bleeding complications were documented. Most patients had no evidence of underlying thrombophilia (n=15); for those with positive hypercoagulability screens, the most common positive marker was the presence of lupus inhibitor (n=6). Venous thrombosis resulting from adjacent otolaryngologic infection is a serious complication requiring proper recognition and management. The involved vasculature and cranial nerve findings are dependent on the anatomic location of the underlying infection. Cranial neuropathies in the presence of these infections should prompt evaluation for possible thrombosis.

Sex Differences in Outcomes After Transcatheter Aortic Valve Replacement: A POPular TAVI Subanalysis

BackgroundStroke and bleeding are complications after transcatheter aortic valve replacement (TAVR). A higher incidence of bleeding and stroke has been reported in women, but the role of antithrombotic management pre- and post-TAVR has not been studied. ObjectivesThe study sought to compare bleeding and ischemic complications after TAVR between women and men stratified by antiplatelet and oral anticoagulant (OAC) regimen. MethodsThe POPular TAVI (Antiplatelet Therapy for Patients Undergoing Transcatheter Aortic Valve Implantation) trial was a randomized clinical trial to test the hypothesis that monotherapy with aspirin or OAC after TAVR is safer than the addition of clopidogrel. The primary endpoints of interest of this post hoc subanalysis were: 1) all bleeding; and 2) a composite of ischemic events consisting of stroke and myocardial infarction. Secondary endpoints were: 1) nonprocedural bleeding; 2) major or life-threatening bleeding; 3) minor bleeding; 4) stroke; 5) myocardial infarction; and 6) all-cause death. ResultsA total of 978 patients (466 [47.6%] women) were included in this study. All bleeding and the composite of myocardial infarction and stroke rates were similar between sexes (all bleeding: 106 [22.8%] women vs 121 [23.6%] men; P = 0.815; ischemic events: 26 [5.6%] vs 36 [7.0%]; P = 0.429). However, major or life-threatening bleeding occurred more often in women (58 [12.5%]) vs men (38 [7.4%]) (P = 0.011), most of which were access site bleedings. The use of aspirin pre- and post-TAVR increased major or life-threatening bleeding in women but not in men. ConclusionsAfter TAVR, overall bleeding and ischemic outcomes were similar between women and men. However, women had more major or life-threatening bleedings, especially those receiving aspirin pre- and post-TAVR.

CE-454611-3 HIGH RISK LEFT ATRIAL APPENDAGE CLOSURE IN PATIENTS WITH A PERSISTENT LEFT ATRIAL APPENDAGE THROMBUS

Left atrial appendage closure (LAAC) in patients with a persistent left atrial appendage (LAA) thrombus is controversial. To introduce a novel utilization of a cerebral protection device during high risk LAAC in patients with a persistent LAA thrombus. N/A Case 1: A 50-year-old male with persistent atrial fibrillation (AF) and remote left ventricular thrombus with a thromboembolic stroke presented for an AF ablation. He was found to have a persistent LAA thrombus on multiple pre-operative CT scans despite changing anticoagulation regimen with rivaroxaban and subsequently warfarin with aspirin. The ablation was aborted. He underwent LAAC (Watchman FLXTM, Boston Scientific) with the cerebral protection device (SentinelTM, Boston Scientific) in place. The transesophageal echocardiogram during the procedure confirmed persistent LAA thrombus (Figure A). At the end of the procedure, embolic debris were identified within the SentinelTM (Figure B). The patient was discharged with no neurologic symptoms at the time of discharge and remains neurologically intact 10 months post procedure. Case 2: A 68-year-old female with persistent AF on a therapeutic warfarin dose presented for an AF ablation. She was noted to have a LAA thrombus on the pre-operative CT scan and the procedure was aborted. Her anticoagulation was switched to apixaban. A repeat CT revealed no change in LAA thrombus, and more aggressive anticoagulation was limited by hematuria. Therefore, she underwent LAAC with the SentinelTM for cerebral protection. Of note, the intraoperative TEE revealed filamentous LAA thrombus (Figure C). The patient tolerated the procedure well and was safely discharged the following day. She had no post-operative changes in her neurologic status and the Watchman FLXTM on routine TEE remained in stable position (Figure D). The presence of LAA thrombus is a common concern in patients referred for LAAC. While classically avoided, this case series suggests that a thrombus being present is not a contraindication for LAAC. A cerebral protection device may be used to prevent cardioembolic stroke in selected patients with a persistent LAA thrombus. Further studies are needed to determine the safety and efficacy of this strategy.

D27. Effect of Postoperative Anticoagulation Regimen on Lower Extremity Free Flap Outcomes

PURPOSE: Free flap reconstruction for lower extremity (LE) trauma has a higher failure rate than in other anatomic regions. Anticoagulation selection in the immediate postoperative period may influence free flap outcomes. This study evaluates complication rates associated with varying anticoagulation protocols among LE free flap reconstruction. METHODS: Patients with LE trauma with free flap reconstruction from 2016-2021 were included for retrospective chart review. Complications were divided into major (hematoma, flap thrombosis, flap necrosis >10%, infection requiring reoperation) and minor (wound dehiscence, flap necrosis <10%, infection treated with antibiotic alone) categories. Patients were categorized into 4 groups based on postoperative anticoagulation regimen (aspirin, heparin drip, aspirin + heparin drip, and DVT-prophylaxis only). Complication rates were compared between each group. Univariate analysis was performed using ANOVA and chi-squared tests. Multivariable analysis was performed with a generalized linear model to predict any major complications. P values were set at P<0.05. RESULTS: Of 199 patients, 18.6% received aspirin only, 38.2% received heparin drip only, 39.2% received aspirin + heparin drip, and 4.0% received DVT prophylaxis only. Demographics were similar between the groups. Major complication rates were negatively correlated with the aspirin group (p=0.001) and the heparin drip group (p=0.031). CONCLUSION: In patients with LE free tissue transfer after acute trauma, postoperative use of aspirin only or heparin drip only results in fewer complications than aspirin + heparin drip or DVT-prophylaxis alone.

Managing Recurrent Ischemic Cerebrovascular Events in Patients with Atrial Fibrillation Compliant with Oral Anticoagulant Therapy (P6-5.001)

<h3>Objective:</h3> To evaluate if oral anticoagulant therapy change (OAC change) or adding antiplatelet therapy to anticoagulation (AC+AP) in patients with nonvalvular atrial fibrillation (AF) and acute ischemic stroke (AIS) or transient ischemic attack (TIA) despite OAC compliance, is associated with lower risk of recurrent cerebrovascular events compared to patients that continued the same anticoagulant regimen. <h3>Background:</h3> Patients with AF still have an appreciable risk of AIS or TIA despite compliance with OAC. Yet little is known about the best management options in this population. <h3>Design/Methods:</h3> We reviewed all consecutive patients with AF on OAC that presented with AIS/TIA to our tertiary academic stroke center between 2011–2021. Baseline characteristics, type of index event, antithrombotic therapy before and after index event, subsequent recurrent AIS/TIA or major bleeding events were extracted. Fisher’s exact or Log-rank tests and logistic regression models were used to compare outcomes between OAC unchange vs OAC change, and AC+AP vs AC only groups. <h3>Results:</h3> 185 patients (mean age 78.3 ± 12 years) were included. 61% were males and 79 (42.7%) had AIS at index event. 17 (9%) had OAC change and 100 (79%) received AP+AC. 39 (21.15%) had recurrent AIS/TIA, and 28 (15.1%) had major bleeding following the index event. No significant difference was observed between OAC unchange versus OAC change groups regarding recurrent AIS/TIA (HR = 0.607, 95% CI: 0.229–1.609, p = 0.316) or major bleeding events (OR = 1.541, 95% CI: 0.391–10.299, p = 0.586). Additionally, no significant difference was observed between AC+AP versus AC groups regarding recurrent AIS/TIA (HR= 0.863, 95% CI: 0.430–1.732, p = 0.679) or major bleeding events (OR= 0.894, 95% CI: 0.377–2.135, p = 0.798). <h3>Conclusions:</h3> In patients with AF and acute ischemic cerebrovascular events despite OAC compliance, changing anticoagulant or adding antiplatelet agent may not decrease risk of future cerebrovascular events. <b>Disclosure:</b> Dr. Harahsheh has nothing to disclose. Mr. Elshaigi has nothing to disclose. Dr. Alhayek has nothing to disclose. Vanesa Vanderhye has nothing to disclose. Dr. O’Carroll has nothing to disclose. Dr. Dumitrascu has nothing to disclose.

Intravenously administered APAC, a dual AntiPlatelet AntiCoagulant, targets arterial injury site to inhibit platelet thrombus formation and tissue factor activity in mice

IntroductionArterial thrombosis is the main underlying mechanism of acute atherothrombosis. Combined antiplatelet and anticoagulant regimens prevent thrombosis but increase bleeding rates. Mast cell-derived heparin proteoglycans have local antithrombotic properties, and their semisynthetic dual AntiPlatelet and AntiCoagulant (APAC) mimetic may provide a new efficacious and safe tool for arterial thrombosis. We investigated the in vivo impact of intravenous APAC (0.3–0.5 mg/kg; doses chosen according to pharmacokinetic studies) in two mouse models of arterial thrombosis and the in vitro actions in mouse platelets and plasma. Materials and methodsPlatelet function and coagulation were studied with light transmission aggregometry and clotting times. Carotid arterial thrombosis was induced either by photochemical injury or surgically exposing vascular collagen after infusion of APAC, UFH or vehicle. Time to occlusion, targeting of APAC to the vascular injury site and platelet deposition on these sites were assessed by intra-vital imaging. Tissue factor activity (TF) of the carotid artery and in plasma was captured. ResultsAPAC inhibited platelet responsiveness to agonist stimulation (collagen and ADP) and prolonged APTT and thrombin time. After photochemical carotid injury, APAC-treatment prolonged times to occlusion in comparison with UFH or vehicle, and decreased TF both in carotid lysates and plasma. Upon binding from circulation to vascular collagen-exposing injury sites, APAC reduced the in situ platelet deposition. ConclusionsIntravenous APAC targets arterial injury sites to exert local dual antiplatelet and anticoagulant actions and attenuates thrombosis upon carotid injuries in mice. Systemic APAC provides local efficacy, highlighting APAC as a novel antithrombotic to reduce cardiovascular complications.

Outcomes of patients with atrial fibrillation and ischemic stroke while on oral anticoagulation.

The prognosis of patients with atrial fibrillation (AF) and ischemic stroke while taking oral anticoagulation is poorly understood. This study aimed to characterize the outcomes of patients following a stroke event while on oral anticoagulation. Individual participant data from five pivotal randomized trials of antithrombotic therapy in AF were used to assess the outcomes of patients with a post-randomization ischemic stroke while on study medication (warfarin, standard-, or lower-dose direct oral anticoagulant regimen) during trial follow-up. The primary outcome was recurrent ischemic stroke after the first post-randomization ischemic stroke. The primary analysis included 1163 patients with a first post-randomization ischemic stroke while on study medication (median age 73 years, 39.3% female, 35.4% history of stroke before trial enrollment). During a median continued follow-up of 337 days, 74 patients had a recurrent ischemic stroke [cumulative incidence at 1 year: 7.0%, 95% confidence interval (CI) 5.2%-8.7%]. The cumulative incidence of mortality at 3 months after stroke was 12.4% (95% CI 10.5%-14.4%). Consistent results for the incidence of recurrent ischemic stroke at 1 year were obtained in an analysis accounting for the competing risk of death (6.2%, 95% CI 4.8%-7.9%) and in a landmark analysis excluding the first 2 weeks after the index stroke and only including patients without permanent study drug discontinuation since then (6.8%, 95% CI 4.6%-8.9%). Patients with AF and ischemic stroke while on oral anticoagulation are at increased risk of recurrent ischemic stroke and death. These patients currently have an unmet medical need.

The effects of differing anticoagulant regimes on blood quality after cell salvage in coronary artery bypass grafting (CABG): a pilot study

BackgroundCell salvage reduces allogenic blood transfusion requirements in surgery. We present a pilot study exploring the impact of anticoagulant choice, citrate or heparin, on the quality of cell salvaged blood in adults undergoing coronary artery bypass grafting (CABG).Materials and methodsElective on pump CABG patients were randomly allocated to citrate or heparin anticoagulation. We measured red blood cell characteristics and inflammation in both the blood collection reservoir and the washed red blood cell concentrate. Postoperatively, the level of biomarkers and the coagulation profile in the peripheral blood as well as the transfusion requirements of allogenic blood products were studied.ResultsThirty eight patients were included, 19 in the citrate group and 19 in the heparin group. Baseline characteristics were similar. In the washed red blood cell concentrate, Mean Hb (g/dl) and Ht (%) were lower in the citrate group [Hb: 18.1 g/dL (SD 1.3) vs. 21.1 (1.6), p < 0.001; Ht: 59.9% (54.7–60.9) vs. 63.7% (62.3–64.8); p < 0.001]; Mean corpuscular volume (MCV, μm 3) was higher [99.1fL (9.4) vs. 88 (4.2), p < 0.001] and mean corpuscular hemoglobin concentration (MCHC, g/dl) lower in the citrate group [31.9 g/dl (29.6–32.4) vs. 33.6 (33.1–34.0) p < 0.001]. Thrombocyte count (1000/μl) was higher in the citrate group [31.0 (26.0–77.0) vs. 13.0 (10.0–39.0); p = 0.006]. There were no differences in the requirement for allogenic blood products’ transfusion (intraoperatively and postoperatively) or in the coagulation parameters after washed red blood cell concentrate infusion. Higher IL-10 was found in the citrate group in the blood collection reservoir, higher neutrophil-derived myeloperoxidase (MPO) in the heparin group after washed red blood cell concentrate infusion.ConclusionThough red blood cells in washed red blood cell concentrate were more swollen and diluted in the citrate group with more residual thrombocytes, published quality guidelines were met in both groups. Our pilot study suggests that differences in inflammatory markers in the blood collection reservoir and after infusion of washed red blood cell concentrate indicate a possible pro-inflammatory effect of heparin compared to citrate. A larger study is warranted to confirm these results and their possible clinical consequences.Trial registrationClinicalTrials.gov: NCT02674906. Registered 5 February 2016.

Incidence of deep venous thrombosis in COVID-19 critically ill patients treated with intermediate-dose of heparin for thromboprophylaxis: The COVIDOP-DVT observational study.

The high prevalence of deep vein thrombosis (DVT) in patients admitted to intensive care unit (ICU) for COVID-19-related acute respiratory distress syndrome (ARDS) would justify systematic screening of these patients or higher therapeutic dose of heparin for thromboprophylaxis. We performed a systematic echo-Doppler of the lower limb proximal veins during the first 48 h (visit 1) and from 7 to 9 days after visit 1 (visit 2) in consecutive patients admitted to the ICU of a university-affiliated tertiary hospital for severe proven COVID-19 during the second wave. All patients received intermediate-dose heparin (IDH). The primary objective was to determine DVT incidence on venous Doppler ultrasound. Secondary objectives were to determine whether the presence of DVT modifies the anticoagulation regimen, the incidence of major bleeding according to International Society on Thrombosis and Haemostasis (ISTH) criteria, and the mortality rate of patients with and without DVT. We included 48 patients (30 [62.5%] men) with a median age of 63 years [IQR, 54-70]. The prevalence of proximal deep vein thrombosis was 4.2% (2/48). In these two patients, after DVT diagnosis, anticoagulation was changed from intermediate to curative dose. Two patients (4.2%) had a major bleeding complication according to ISTH criteria. Among the 48 patients, 9 (18.8%) died before hospital discharge. No DVT or pulmonary embolism was diagnosed in these deceased patients during their hospital stay. In critically ill patients with COVID-19, management with IDH results in a low incidence of DVT. Although our study is not designed to demonstrate any difference in outcome, our results do not suggest any signal of harm when using intermediate-dose heparin (IDH) COVID-19 with a frequency of major bleeding complications less than 5%.

British Society for Haematology guideline for anticoagulantmanagement of pregnant individuals with mechanical heart valves.

British Society for Haematology guideline for anticoagulantmanagement of pregnant individuals with mechanical heart valves.