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The recent Academic Research Consortium for High Bleeding Risk (ARC-HBR) proposal did not consider acute coronary syndrome (ACS), by consensus, a bleeding criterion per se despite being a high bleeding risk (HBR) scenario. We investigated the applicability of the ARC-HBR classification and criteria in ACS patients.Patients with ACS undergoing coronary stenting between 2012 and 2018 at a tertiary hospital were retrospectively classified as being at HBR if they met ≥ 1 major or ≥ 2 minor ARC-HBR criteria. The primary endpoint was the 1-year cumulative incidence of Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding.Among 4412 patients, 29.5% were at HBR. The incidence of bleeding was higher in the HBR group than in the non-HBR group (9.4% vs 1.3%; P.01). The rates of in-hospital periprocedural and postdischarge bleeding were also higher in the HBR group (4.3% vs 0.5% and 5.3% vs 0.9%, respectively; P.01). Bleeding risk gradually increased with increasing ARC-HBR criteria: 1.8%, 5.0%, 9.4%, 16.8%, 25.2%, and 25.9% for 1 isolated minor criterion, ≥ 2 isolated minor criteria, 1 major criterion (isolated or plus 1 minor criterion), 1 major plus ≥ 2 minor criteria, ≥ 2 major criteria (isolated or plus 1 minor criterion), and ≥ 2 major plus ≥ 2 minor criteria, respectively. Sixteen (80%) out of 20 ARC-HBR criteria satisfied the ARC-HBR predefined cutoffs for BARC 3 or 5 bleeding risk.This study supports the use of the ARC-HBR classification and criteria in the ACS setting. The ARC-HBR classification provides an accurate major bleeding risk estimate and it seems suitable for the identification and management of patients at HBR.

Anomalies of the inferior vena cava pose a great challenge to surgeons. Although uncommon, these congenital vascular malformations may have significant surgical implications. Awareness of their presence is essential to avoid inadvertent injury and major bleeding during retroperitoneal procedures. An accurate preoperative diagnosis and detailed planning play a crucial role to obtain successful outcomes when confronted with them. Several surgical techniques have been recommended to protect these anomalous venous structures. The aim of this review is to contribute to the knowledge of the most common types of anomalies of inferior vena cava encountered during retroperitoneal procedures. With this purpose, a summary of their anatomy, embryology, incidence, diagnosis and intra-operative management is presented.

Introduction: Nephrologists have recently recognized the heterogeneity of kidney diseases among patients with diabetes and begun to actively perform percutaneous renal biopsies (PRBs). Nevertheless, the association between diabetes and major bleeding complications of PRB remains unclear. Methods: In this retrospective cohort study using the Diagnosis Procedure Combination database in Japan, we identified patients who underwent an elective PRB from July 2010 to March 2018. The primary outcome was the occurrence of major bleeding complications, defined as red blood cell transfusion within 7 days after PRB or invasive hemostasis after PRB. Multivariable regression analysis was performed to analyze the association between diabetes and major bleeding complications with adjustment for patient and hospital characteristics. Results: We identified 76,302 patients, including 8245 with diabetes. The proportion of PRBs performed for patients with diabetes continuously increased over time. Major bleeding complications occurred in 678 patients (0.9%), including 622 (0.8%) with red blood cell (RBC) transfusion and 109 (0.1%) with invasive hemostasis. Diabetes was significantly associated with major bleeding complications (relative risk [RR] = 2.41; 95% CI 2.00–2.90). Among patients with diabetes, multiagent or insulin treatment had significant association with major bleeding complications (RR = 1.57; 95% CI 1.18–2.10), compared with single-agent diabetes treatment. Conclusion: Diabetes is significantly associated with major bleeding complications of PRBs. Moreover, severity of diabetes has association with increases in major bleeding complications. Thus, nephrologists should carefully judge whether the anticipated benefits outweigh the relatively high risk of major bleeding complications when considering PRB for patients with diabetes.

To examine the association between inferior vena cava (IVC) diameter and postpartum blood loss and assess whether IVC diameter is a useful marker in the evaluation of intravascular volume status in women with postpartum hemorrhage (PPH).This was a prospective case-control study conducted in a university medical teaching center in Afula, Israel, between November 2018 and March 2020. The study cohort consisted of women with a singleton pregnancy who delivered vaginally at term. The PPH group included women diagnosed with PPH based on visually estimated blood loss of 1000 mL or more at the time of enrolment. Hemodynamically unstable women or women with major bleeding at the time of diagnosis were not included. The control group consisted of women with an uneventful fourth stage of labor. IVC diameter was measured using transabdominal ultrasonography during inspiration (IVCi diameter) and expiration (IVCe diameter), and the collapsibility index was calculated ((IVCe - IVCi)/IVCe × 100). The primary outcome was the percentage difference in IVC diameter and collapsibility index between the PPH group and controls. The performance of the IVC collapsibility index in the prediction of the need for blood transfusion in women with PPH was assessed. In order to demonstrate a difference of 20% with a power of 80% and alpha of 0.05, 108 women, at a ratio of 1:2 in the study and control groups, respectively, were needed.Overall, 36 and 72 women were included in the final analysis in the PPH and control groups, respectively. IVCi and IVCe diameters were significantly smaller in the PPH group (0.93 ± 0.30 cm and 1.26 ± 0.32 cm, respectively) than in controls (1.42 ± 0.31 cm and 1.75 ± 0.28 cm, respectively) (P = 0.001 for both). The percentage reductions in IVCi and IVCe diameters in the PPH group compared with controls were 35.0% and 28.0%, respectively. IVC collapsibility index was increased significantly, by 42.9% (26.04 ± 8.67% vs 18.15 ± 5.07%; P = 0.001) in the PPH group compared with controls. IVC collapsibility index was a significant predictor of the need for blood transfusion and correctly predicted 81% of cases. Logistic regression analysis demonstrated that IVC collapsibility index was also a significant predictor of a drop in hemoglobin level of ≥ 2 g/dL (P = 0.001).IVC diameter changes in response to postpartum blood loss. Measurement of IVC diameter using transabdominal ultrasonography is an objective and useful non-invasive method for the early evaluation of intravascular volume status in women with PPH and for the prediction of cases that might require blood transfusion. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Evidence on the efficacy and safety of low-dose direct oral anticoagulant (DOAC) in older patients with nonvalvular atrial fibrillation is still scarce. We conducted a single-center prospective registry of patients with nonvalvular atrial fibrillation treated with DOACs: the DIRECT registry (n = 2,216; follow-up, 407 ± 388 days, UMIN000033283). The whole population was divided into 2 groups: the older group (age ≥80 years, n = 548) versus the younger group (age80 years, n = 1,668). Primary safety and efficacy end points were major bleeding according to the International Society on Thrombosis and Haemostasis criteria, and stroke or systemic embolism (SSE), respectively. Effects of known risk factors and low-dose DOAC on major bleeding and SSE were assessed using a multivariable Cox proportional hazards model. In the older group, low-dose DOAC was associated with lower bleeding events (hazard ratio 0.279, 95% confidence interval 0.087 to 0.892, p = 0.031) but was not associated with increased SSE (p = 0.894). In the younger group, low-dose DOAC was neither associated with risk of major bleeding nor SSE (both p 0.05). In conclusion, in older patients, low-dose DOAC was associated with reduced risk of major bleeding without compromising its efficacy.

Introduction and aim Portal vein thrombosis (PVT) is associated with a higher risk of liver-related complications. Recent guidelines recommend direct-acting anticoagulants (DOAC) in patients with cirrhosis and non-tumoral PVT. However, data on the efficacy and safety of DOAC in these patients remain limited. We aim to investigate the efficacy and safety of DOAC compared to vitamin K antagonists (VKA) to treat non-tumoral PVT in patients with cirrhosis. Methods We performed a systematic search of six electronic databases using MeSH term and free text. We selected all studies comparing the use of DOACs with vitamin K antagonist to treat PVT in cirrhosis. The primary outcome was PVT recanalization. Secondary outcomes were and PVT progression, major bleeding, variceal bleeding and death. Results From 944 citations, we included 552 subjects from a total of 11 studies (10 observational and 1 randomized trial) that fulfilled the inclusion criteria. We found that DOAC were associated with a higher pooled rate of PVT recanalization (RR = 1.67, 95%CI: 1.02, 2.74, I2 = 79%) and lower pooled risk of PVT progression (RR = 0.14, 95%CI: 0.03–0.57, I2 = 0%). The pooled risk of major bleeding (RR = 0.29, 95%CI: 0.08–1.01, I2 = 0%), variceal bleeding (RR = 1.29, 95%CI: 0.64–2.59, I2 = 0%) and death (RR = 0.31, 95%CI: 0.01–9.578, I2 = 80%) was similar between DOAC and VKA. Conclusion For the treatment of PVT in patients with cirrhosis, the bleeding risk was comparable between DOAC and VKA. However, DOAC were associated with a higher pooled rate of PVT recanalization. Dedicated randomized studies are needed to confirm these findings.

Objective We sought to identify the factors associated with a worse prognosis in Emergency Department (ED) patients with atrial fibrillation (AF), crucial information to guide management decisions. Methods This is a secondary analysis of a prospective, multicenter, observational cohort of consecutive AF patients attended in 62 EDs in Spain. Clinical variables were collected on enrollment. Follow-up was performed at 30 days and one year. The primary composite outcome was all-cause mortality, major bleeding and/or stroke at one year. Secondary outcomes were each of these components considered separately, plus one-year cardiovascular mortality and the composite outcome at 30 days. Results We analyzed 1107 patients. The primary outcome occurred in 209 patients (18.9%), one-year all-cause mortality in 151 (13.6%), major bleeding in 47 (4.2%), and stroke in 31 (2.8%). Disability (HR 2.064, 95% CI 1.478–2.882), previous known AF (HR 1.829, 95% CI 1.096–3.051), long duration of the AF episode (HR 1.849, 95% CI 1.052–3.252) and renal failure (HR 2.073, 95% CI 1.433–2.999) were independently associated with the primary outcome, whereas anticoagulation at discharge was inversely associated (HR 0.576, 95% CI 0.415–0.801). Disability was associated with mortality, cardiovascular mortality, and the composite at 30 days, and renal failure with mortality and major bleeding. Conclusions Comorbidities like renal failure, long AF duration and disability were related to adverse outcomes and should be decisive to guide management decisions in ED patients with AF. Anticoagulation had a positive impact on prognosis and should be the mainstay of therapy in AF patients attended in ED.

The optimal duration of dual antiplatelet therapy (DAPT) for patients implanted with new-generation drug-eluting stents in East Asians is currently still controversial. The purpose of this meta-analysis was to investigate the efficacy and safety of short-term DAPT in patients with those. In this study, randomized controlled trials from PubMed, EMBASE, and Cochrane Library were searched to compare the efficacy and safety of short-term DAPT (6 months or less) with long-term DAPT (12 months or more) in patients implanted with new-generation drug-eluting stents in East Asian from inception to September 2020. The primary efficacy outcome was all-cause death, the primary safety outcome was major bleeding, and the secondary outcomes included cardiovascular death, myocardial infarction, definite or possible stent thrombosis, and stroke. A total of 6 randomized controlled trials with 15,688 patients met inclusion criteria; there were no significant differences in the incidence of all-cause death [risk ratio (RR), 1.03; 0.76-1.39; P = 0.856)], cardiovascular death (RR, 0.83; 0.55-1.24; P = 0.361), myocardial infarction (RR, 0.97; 0.72-1.31; P = 0.853), definite or possible stent thrombosis (RR, 1.52; 0.83-2.78; P = 0.170), and stroke (RR, 0.90; 0.61-1.31; P = 0.574) between short-term and long-term DAPTs. However, there was a significant difference in the risk of major bleeding (RR, 0.64; 0.49-0.85; P = 0.002) between the 2 groups. Compared with long-term DAPT, the short-term DAPT can reduce the risk of major bleeding without increasing the risk of death or ischemia for East Asians (Registered by PROSPERO, CRD42020213266).

Objective The optimal intensity of anticoagulation for adult patients supported with extracorporeal membrane oxygenation (ECMO) remains uncertain. The objective of this study was to evaluate the effectiveness and safety of two anticoagulation protocols using conventional (0.3-0.7 IU/ml) versus restricted (0.2-0.5 IU/ml) anti-factor Xa (anti-Xa) targets for the management of unfractionated heparin (UFH) in adult ECMO patients. Methods This retrospective before-after cohort study compared two groups of ECMO patients who received UFH for at least 24-h from March 2016 to May 2019. The primary outcome was the composite rate of major bleeding or thrombotic events per ECMO day. Secondary outcomes included the mean amount of blood products transfused per ECMO day, the proportion of patients who were within the target anti-Xa at 24-h, the time to achieve target anti-Xa, and the number of heparin infusion adjustments to reach target anti-Xa. Results Forty-one patients were included in this analysis (conventional, n = 25; restricted, n = 16). There was no difference in the composite rate of major bleeding or thrombotic events per ECMO day (p = .090). The restricted group had lower rates of packed red blood cells (pRBC) transfusion per ECMO day (mean 1 ± 1 vs 3 ± 2 units, p = .003) and required fewer heparin infusion adjustments to reach the target (p = .007). There was no difference between the groups in the number of patients who achieved target anti-Xa at 24-h (p = .940). Conclusion In adult ECMO patients, anticoagulation with a restricted anti-Xa target was associated with lower pRBC transfusions and did not provoke an excess of thrombotic events.

Background: Endovascular stenting of the deep venous system has been proposed as a method to treat patients with symptomatic iliofemoral outflow obstruction. The purpose of this systematic review and meta-analysis was to compare the effectiveness of this treatment at 1-year following the development of dedicated venous stents. Method and results: We searched MEDLINE and EMBASE for studies evaluating the effectiveness of venous stent placement. Data were extracted by disease pathogenesis: non-thrombotic iliac vein lesions (NIVL), acute thrombotic (DVT), or post-thrombotic syndrome (PTS). Main outcomes included technical success, stent patency at 1 year and symptom relief. A total of 49 studies reporting outcomes in 5154 patients (NIVL, 1431; DVT, 950; PTS, 2773) were included in the meta-analysis. Technical success rates were comparable among groups (97%-100%). There were no periprocedural deaths. Minor bleeding was reported in up to 5% of patients and major bleeding in 0.5% upon intervention. Transient back pain was noted in 55% of PTS patients following intervention. There was significant heterogeneity between studies reporting outcomes in PTS patients. Primary and cumulative patency at 1 year was: NIVL—96% and 100%; DVT—91% and 97%; PTS (stents above the ligament)—77% and 94%, and; PTS (stents across the ligament)—78% and 94%. There were insufficient data to compare patency outcomes of dedicated and nondedicated venous stents in patients with acute DVT. In NIVL and PTS patients, stent patency was comparable at 1 year. There was inconsistency in the use of validated tools for the measurement of symptoms before and after intervention. When reported, venous claudication, improved in 83% of PTS patients and 90% of NIVL patients, and ulcer healing occurred in 80% of PTS patients and 32% of NIVL patients. Conclusions: The first generation of dedicated venous stents perform comparably in terms of patency and clinical outcomes to non-dedicated technologies at 1 year for the treatment of patients with NIVL and PTS. However, significant heterogeneity exists between studies and standardized criteria are urgently needed to report outcomes in patients undergoing deep venous stenting.

Background Improved prediction of the risk of early major bleeding in pulmonary embolism (PE) is needed to optimize acute management. Research Question Does a simple scoring system predict early major bleeding in acute PE patients, identifying patients with either high or low probability of early major bleeding? Study Design and Methods From a multicenter prospective registry including 2,754 patients, we performed post hoc multivariable logistic regression analysis to build a risk score to predict early (up to hospital discharge) major bleeding events. We validated the endpoint model internally, using bootstrapping in the derivation dataset by sampling with replacement for 500 iterations. Performances of this novel score were compared with that of the VTE-BLEED (Venous Thrombo-Embolism Bleed), RIETE (Registro informatizado de la enfermedad tromboembolica en Espana; Computerized Registry of Patients with Venous Thromboembolism), and BACS (Bleeding, Age, Cancer, and Syncope) models. Results Multivariable regression identified three predictors for the occurrence of 82 major bleeds (3.0%; 95% CI, 2.39%-3.72%): Syncope (+1.5); Anemia, defined as hemoglobin 2.5 points). Observed bleeding rates increased with increasing risk group, from 0.97% (95% CI, 0.53%-1.62%) in the low-risk to 8.93% (95% CI, 6.15%-12.44%) in the high-risk group. C-index was 0.74 (95% CI, 0.73-0.76) and Brier score 0.028 in the derivation cohort. Similar values were calculated from internal bootstrapping. Performance of the PE-SARD score was better than that observed with the VTE-BLEED, RIETE, and BACS scores, leading to a high proportion of bleeding-risk reclassification in patients who bled and those who did not. Interpretation The PE-SARD bleeding risk score is an original, user-friendly score to estimate risk of early major bleeding in patients with acute PE.

ARTS will be the first trial to compare anticoagulation with a direct oral anticoagulant (apixaban) versus no anticoagulation among patients undergoing intra-abdominal, gynecologic, or urologic surgery at sufficiently similar risk of deep vein thrombosis or pulmonary embolism and major bleeding.

PURPOSE Data regarding post-procedural antithrombotic therapy following percutaneous left atrial appendage (LAA) in real-world populations using various occluder systems is limited. In the present analysis, anticoagulation (AC) was compared against antiplatelet therapy (APT) using data from the real-world multi-center LAARGE study. METHODS Patients following LAA closure enrolled in the LAARGE study were assigned to two groups depending on initial post-implantation antithrombotic regime consisting of either AC or APT. Selection of antithrombotic medication was at the discretion of the treating center and/or physician. RESULTS From July 2014 until January 2016, a total of 627 patients at 38 centers were included. A total of 75 patients (12%) received AC and 552 patients (88%) received APT, respectively. No significant differences were found between the groups regarding the composite of death, stroke and systemic embolism 1 year after LAA closure (Kaplan-Meier estimated rate 9.4% for AC vs. 12.8% for APT; p log rank = 0.45). With respect to bleeding events also, no differences were observed 1 year after the procedure (major bleeding 4.0% vs. 2.0%, p = 0.23; moderate bleeding 4.0% vs. 4.9%, p = 1.00; any bleeding 8.0% vs. 6.9%, p = 0.73). CONCLUSIONS Postprocedural antithrombotic treatment with AC and APT showed comparable results regarding the composite of death, stroke, and systemic embolism as well as regarding bleeding complications after LAA closure in a real-world all-comers population.

PURPOSE OF REVIEW Major bleeding in cardiac surgery is commonly encountered, and, until recently, most frequently managed with fresh frozen plasma (FFP). However, a Cochrane review found this practice to be associated with a significant increase in red blood cell (RBC) transfusions and costs. These findings have led to off-label uses of prothrombin complex concentrates (PCCs) in cardiac surgery. The purpose of this review is to compare and contrast the use of FFP and PCC, review the components, limitations and risks of different types of PCCs, and discuss the latest evidence for the use of PCC versus FFP in cardiac surgery. RECENT FINDINGS A recent review and meta-analysis suggests that PCC administration in cardiac surgery is more effective than FFP in reducing RBC transfusions and costs. SUMMARY The current data supports the use of 4F-PCC instead of FFP as the primary hemostatic agent in cases of major bleeding in cardiac surgery. The use of PCCs is associated with reduced rates of RBC transfusions while maintaining a favorable safety profile. Clear advantages of PCC over FFP include its smaller volume, higher concentration of coagulation factors and shorter acquisition and administration times.

BACKGROUND AND AIM The RHEMITT score (Renal disease; Heart failure; Endoscopic findings; Major bleeding; Incomplete SBCE; Tobacco; Treatment by enteroscopy) was the first score to accurately predict the individual risk of small bowel rebleeding after capsule endoscopy (SBCE). The aim of the study is on the prospective validation of the RHEMITT score. METHODS Cohort of consecutive patients with mid-gastrointestinal bleeding (MGIB) submitted to SBCE and followed prospectively, during at least 12 months, since 2017 until 2020. Rebleeding was defined as an overt bleeding event (melena or hematochezia) or a hemoglobin decrease of at least 2 g/dL. The RHEMITT score was calculated for each patient and the rebleeding rates compared. The performance of the score was tested by calculating the area under curve of the receiver operator characteristic curve. A rebleeding-free survival was assessed, corresponding to the period between the date of SBCE and the date of the first post-SBCE rebleeding event. RESULTS We included 162 patients, 102 (62.9%) were female, with a mean age of 64 years old. The sensitivities and specificities of the score grades for predicting rebleeding were as following: for low-risk patients, 0% (0-10%) and 28.8% (21.1-36.5%); for intermediate-risk patients, 23.3% (8.2-38.4%) and 72% (64.3-79.7%); for high-risk patients, 76.7% (61.6-91.8%) and 99.2% (97.7-100%), corresponding to an area under curve of the receiver operator characteristic of 0.988 (P

Thrombotic antiphospholipid syndrome (TAPS) is an autoimmune disorder that manifests with venous thromboembolism (VTE) and/or arterial thromboembolism (ATE) in the presence of persistent antiphospholipid antibodies (aPLs). Recent trials have failed to demonstrate non-inferiority of the direct oral anticoagulants (DOACs) compared to vitamin K antagonists as anticoagulation in TAPS, but there is a subgroup of non-triple positive patients without prior ATE in who only limited data exists. The objective of this study was to assess the effectiveness and safety of DOACs in non-triple positive TAPS without prior ATE. We conducted a retrospective review of all non-triple positive TAPS patients without prior ATE who were anticoagulated with a DOAC at two tertiary care hospitals from January 2010 to July 2020. We assessed outcomes of VTE, ATE, major bleeding, and clinically relevant non-major bleeding (CRNMB). 50 patients were included in the analysis, encompassing 157.2 years of patient follow-up. There were no recurrent VTE, but one patient had a possible arterial thrombosis (0.64 events per 100 patient-years [95% confidence interval (CI 0.16-35.49)] as a transient ischemic attack (TIA) which occurred on reduced dose DOAC. There were no major bleeding events, but two patients had CRNMB (1.27 events per 100 patient-years [95% CI 1.5-46.0]), both as menorrhagia. DOACs were effective and safe as anticoagulation in non-triple positive TAPS patients without prior ATE with a low rate of recurrent thrombosis and bleeding. Larger, prospective controlled studies are required to confirm these findings prior to routine use of DOACs in this subgroup.

OBJECTIVE: With the increase in cardiovascular implantable-electronic devices (CIEDs), complications from insertion and healing are also increasing. Therefore, the objective of this study was to compare the intracutaneous stapling method to the absorbable suture technique in terms of complications, procedure time, and pocket closure time. METHODS: An observational study was conducted over the course of three months on patients with CIED implantation. The patients were divided in two groups according to pocket closure technique. Group 1 included patients with pocket closure using intracutaneous sutures; whereas in Group 2, the pocket was closed by intracutaneous staples. Data were collected regarding patient characteristics and wound problems. The endpoints were wound problems, including early and late wound problems (primary), total procedure time, and the time taken for pocket closure (secondary). RESULTS: One hundred and nineteen patients and 107 patients were allocated to Group 1 and Group 2, respectively. During the three-month observation period, 27 (22.6%) patients in Group 1 and 13 (12.1%) patients in Group 2 suffered from early wound problems, and the combined primary endpoint reached was statistically significant (p=0.021). Minor and major bleeding events were more common in Group 1 [Odds ratio (OR): 4.49, p=0.024; OR: 0.96, p=0.052]. The time to close the pocket was markedly reduced in Group 2 (7.29±1.42 vs. 3.98±1.19, p

To assess the impact of elevated blood pressure on the rate of major hemorrhagic complication after renal transplant biopsy. Pre-procedural systolic (SBP), diastolic (SBP), and mean arterial (MAP) blood pressure for consecutive patients undergoing US-guided renal transplant biopsies from 08/01/2015 to 7/31/2017 were retrospectively recorded. Patients who had a major bleeding complication were identified. The risk of complication as a function of SBP, DBP, and MAP was statistically analyzed, with significance set at p

While massive transfusion (MT) recipients account for a small proportion of all transfused patients, they account for approximately 10% of blood products issued. Furthermore, MT events pose organizational and logistical challenges for health care providers, laboratory and transfusion services. Overall, the majority of MT events are to support major bleeding in surgical patients, trauma and gastrointestinal hemorrhage. The clinical context in which the bleeding event occurred, the number of blood products required, patient age and comorbidities are the most important predictors of outcomes for short- and long-term survival. These data are important to inform blood services, clinicians and health care providers in order to improve care and outcomes for patients with major bleeding. There is no standard accepted definition of MT, with most definitions based on number of blood components administered within a certain time-period or activation of MT protocol. The type of definition used has implications for the clinical characteristics of MT recipients included in epidemiological and interventional studies. In order to understand trends in incidence of MT, variation in blood utilization and patient outcomes, and to harmonize research outcomes, a standard and universally accepted definition of MT is urgently required.

Fibrinogen is a key coagulation protein that is necessary for the formation of stable clots. Fibrinogen levels have been reported to be one of the first to fall during major haemorrhage reflecting consumption, dilution and fibrinogenolysis. Its role in acquired major haemorrhage, both in relation to the contribution it plays to the coagulopathy of major bleeding that can exacerbate bleeding and how effective fibrinogen supplementation can be at improving clinical outcomes, has received a great deal of attention over the last 10 - 15 years. This commentary focuses on just three of the more recent publications from the last 5 years that provide some of the evidence behind how we can think about fibrinogen as a haemostatic treatment for acquired major haemorrhage and how we can use the laboratory thresholds to guide therapy.

BACKGROUND: Major bleeding (MB) events are independent predictors of mortality after cardiac interventional procedures. The clinical relevance of MB following left atrial appendage occlusion (LAAO) remains unclear.AIMS: This study aimed to investigate the incidence and clinical impact of MB after LAAO in a real-world population at high risk for bleeding and contraindicated to anticoagulation.METHODS: The two-year results of the Amplatzer Amulet Observational Post-Market Study were analysed. An independent committee adjudicated MBs according to the Bleeding Academic Research Consortium scale. Cox proportional hazards regression identified variables associated with MB events and mortality.RESULTS: The MB rate was 7.2%/year, with a rate of 10.1%/year during year one, decreasing to 4.0%/year over year two. The most common bleeding location was gastrointestinal, accounting for 48% of MBs. Pre-LAAO MB was associated with an increased risk for post-LAAO MB (HR 2.34, 95% CI: 1.37-3.99). The occurrence of post-LAAO MB was associated with increased mortality (37.3% vs 12.7%; pCONCLUSIONS: In real-world patients at high bleeding risk, MB following LAAO was not uncommon and associated with a significant increase in mortality, without increasing the risk of stroke. ClinicalTrials.gov Identifier: NCT02447081. https://clinicaltrials.gov/ct2/show/NCT02447081.

Gastrointestinal (GI) bleeding is the most frequent single site of oral anticoagulant (OAC)-associated major bleeding. Patients with major GI bleeding experience morbidity and a substantial risk of short-term all-cause mortality up to 10%. While OACs are frequently discontinued during acute bleeding, there is substantial uncertainty about whether, when, and how OACs should be resumed after bleeding has resolved. Limited evidence suggests a lower risk of thromboembolism and death, and a higher risk of recurrent bleeding with OAC resumption. However, the absolute risks and optimal timing of anticoagulation remain uncertain based on these observational studies at risk of bias, particularly due to baseline confounding. In addition to an individualized approach to determining the benefits and harms of treatment decisions informed by the best available evidence about thrombosis and recurrent bleeding, discussions should meaningfully incorporate patient values and preferences. The objective of this review is to provide a framework for decision-making by summarizing the epidemiology and clinical outcomes of OAC-associated GI bleeding, providing an approach for assessment and risk stratification for OAC resumption and its timing, and outlining strategies for the prevention of recurrent GI bleeding.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) in patients with coronavirus disease 2019 (COVID-19) showed reasonable outcomes. However, recent studies indicated a negative trend and analysis is needed. METHODS: Baseline characteristics, laboratory parameters, and outcomes of ECMO-supported patients with COVID-19 were analyzed in a retrospective single-center study. We included hospital admissions until February 28, 2021; patients were followed until discharge/death. Eventually, we compared data between patients hospitalized before and after September 1, 2020. RESULTS: Median age of patients treated with ECMO (n=39) was 56 years; most patients were males (n=28, 72%). Median mechanical ventilation time (prior to ECMO) was 6 days, while the median ECMO duration was 19 days. Overall survival rate was 41%. In the sub-analysis, survival until discharge in the first and second epidemic waves was 53% (n=19) and 30% (n=20), respectively (P=0.2). At baseline, compared with patients of the first wave, those of the second wave had higher median body mass index (28.2 vs. 31.1 kg/m(2), respectively, P=0.02), bicarbonate (27 vs. 31.8 mmol/L, respectively, P=0.033), plasma free hemoglobin (36 vs. 58 mg/L, respectively, P=0.013), alanine aminotransferase (33 vs. 52 U/L, respectively, P=0.018), and pH (7.29 vs. 7.42, respectively, P=0.005), lower rate of pulmonary hypertension (32% vs. 0%, respectively, P=0.008), lower positive end-expiratory pressure (14 vs. 12 cmH(2)O, respectively, P=0.04), longer median ECMO duration (16 vs. 24.5 days, respectively, P=0.074), and more frequent major bleeding events (42% vs. 80%, respectively, P=0.022). CONCLUSIONS: ECMO-supported patients with COVID-19 had an overall survival rate of 41%. Similar to international registries, we observed less favorable outcomes during the second wave. Further research is needed to confirm this signal and find predictors for mortality.

Introduction Warfarin is the core component in the management of various thromboembolic disorders, which requires specialized expertise to optimize outcomes. There is limited data comparing a pharmacist vs. a haematologist-managed anticoagulation clinic in our setting, and in the Middle East. We aimed to evaluate the effectiveness and safety of a pharmacist vs. a haematologist-managed anticoagulation clinic in the Ambulatory Care Center at King Abdulaziz Medical City, Jeddah, Saudi Arabia. Methods A retrospective cohort study was conducted from 2016 to 2018, which included adult patients who have been followed-up for at least six months and who received warfarin for an extended period. The primary outcome was the proportion of time the patients in the two arms were in the therapeutic range. The secondary outcomes were the differences in expanded time in the therapeutic range, as well as the frequency of bleeding and thromboembolic events between the two arms. Results We enrolled 104 and 124 patients in the pharmacist and haematologist arms respectively. The median time in the therapeutic range for the pharmacist arm was 71.4%, IQR (60.8–83.8) vs. 65%, IQR (43.5–79.1), in the haematologist arm (p = 0.0049). The median expanded time in the therapeutic range was 86.4%, IQR (77.5–95.3) vs. 81.21%, IQR (67.1–93.3) in the pharmacist vs. haematologist arm (p = 0.015) respectively. Major bleeding events occurred in 5.7 % vs. 3.2 %, and thromboembolic events in 5.7% vs. 4%, in the pharmacist vs. haematologist arm respectively. Conclusions Our results demonstrated that the time in the therapeutic range was significantly higher in the pharmacist arm, with no significant difference in bleeding and thromboembolic events compared to the haematologist arm.

PURPOSE This study aims to validate major bleeding (MB) cases within a cohort of new users of direct oral anticoagulants (DOACs) in Electronic health records (EHRs) from primary care in Spain (BIFAP), introducing more efficient techniques and automating the process of validation in the pharmacoepidemiologic research with EHR data as much as possible. METHODS Registered bleedings were identified in a cohort of new users of DOACs in BIFAP using ICPC 2 and ICD 9 codes; we ascertained these bleedings as MB through a validation strategy based on the MB definition from the International Society on Thrombosis and Hemostasis, which used hospitalization and critical localization as proxies. We assessed hospitalization with hospital discharge information (only available for some years and regions) and a free text-based algorithm created to identify hospitalization in EHR's clinical notes. Incidence rates (IR) of MB were evaluated by bleeding type. RESULTS The study cohort included 104 614 patients, with 274521.5 p-y of follow up. There were 6143 registered bleedings during the study period (519 intracranial bleeding - ICB, 4606 gastrointestinal bleeding - GIB, 1018 extracranial bleeding - ECB), from which 1679 were confirmed as MB (416 ICB, 1086 GIB, and 177 ECB). The free text-based semi-automatic algorithm had moderate recall (0.59), but high specificity (0.99), and precision (0.94). CONCLUSION The combination of hospitalization and critical localization is a valid approach to validate MB in EHRs with incomplete information. The use of more automatic methods for case validation instead of manual review of clinical notes is favored.

Anticoagulation therapy is prescribed for the prevention of recurrence in patients with venous thromboembolism, which could be temporarily interrupted during invasive procedures. The COMMAND VTE Registry is a multicenter registry enrolling 3027 consecutive patients with acute symptomatic VTE in Japan between January 2010 and August 2014. We identified patients who underwent invasive procedures during the entire follow-up period and evaluated periprocedural managements and clinical outcomes at 30 days after invasive procedures. During a median follow-up period of 1213 (IQR: 847–1764) days, 518 patients underwent invasive procedures with the cumulative incidences of 5.8% at 3 months, 11.1% at 1 year, and 24.0% at 5 years. Among 382 patients in high bleeding-risk category of invasive procedures, anticoagulation therapy had been discontinued already in 62 patients (16%) and interrupted temporarily in 288 patients (75%) during the invasive procedures with bridging anticoagulation therapy with heparin in 214 patients (56%). Among 80 patients in low bleeding-risk category, anticoagulation therapy had been already discontinued in 15 patients (19%) and interrupted temporarily in 31 patients (39%) during invasive procedure with bridging anticoagulation therapy with heparin in 17 patients (21%). At 30 days after the invasive procedures, 14 patients (2.7%) experienced recurrent VTE, while 28 patients (5.4%) had major bleeding. This study elucidated the real-world features of peri-procedural management and prognosis in patients with VTE who underwent invasive procedures during follow-up in the large multicenter VTE registry. The 30-day incidence rates of recurrent VTE and major bleeding events were 2.7% and 5.4%.

Supplemental Digital Content is available in the text., The study aim was to examine the impact time in therapeutic range (TTR, International Normalized Ratio [INR] 2.0–3.0) has on survival and adverse events in patients receiving the HeartWare HVAD System in the ENDURANCE and ENDURANCE Supplemental Trials. Evaluable subjects (n = 495) had >1 INR value recorded 1–24 months postimplant and were categorized as: low TTR (10–39%), moderate TTR (40–69%), and high TTR (≥70%). Baseline characteristics, adverse events, and survival were analyzed. Low TTR patients experienced higher rates of major bleeding (1.69 vs. 0.54 events per patient year [EPPY]; p < 0.001), GI bleeding (1.22 vs. 0.38 EPPY; p < 0.001), stroke (0.47 vs. 0.17 EPPY; p < 0.001), thrombus requiring exchange (0.05 vs. 0.01 EPPY; p = 0.02), infection (1.44 vs. 0.69 EPPY; p < 0.001), and renal dysfunction (0.23 vs. 0.05 EPPY; p < 0.001) compared with high TTR. Moderate TTR had higher rates of major bleeding (0.75 vs. 0.54 EPPY; p < 0.001), thrombus requiring exchange (0.05 vs. 0.01 EPPY; p = 0.007), cardiac arrhythmia (0.32 vs. 0.24 EPPY; p = 0.04), and infection (0.90 vs. 0.69 EPPY; p = 0.001) compared with high TTR. Two year survival was greater among moderate and high versus low cohorts (Log-rank p = 0.001). The significant reduction in morbidity and mortality in destination therapy (DT) HVAD patients with well-controlled TTR (≥70%) emphasizes the importance of vigilant anticoagulation management.

Bilateral Sagittal split ramus osteotomy (BSSRO) represents the majority of mandibular osteotomies. Intraoperative risks associated with BSSRO include unfavorable fractures, major bleeding episodes, and inferior alveolar nerve (IAN) and lingual nerve damage. In particular, injury to the IAN during BSSRO is a well-documented complication. However, reports of immediate microneural repair of transected IAN are scarce. In this report, we describe a case of neurosensory disturbance due to transection of the IAN during BSSRO. A 20-year-old woman underwent BSSRO at our hospital. Intraoperatively, the IAN was transected during osteotomy, and immediate microneural repair of the IAN was performed combined with polyglycolic acid (PGA) sheet. We performed the stellate ganglion block (27 times), and prescribed 6.6 mg of dexamethasone sodium phosphate postoperatively from the day of the surgery for 14 days and Vitamin B12 for 6 months postoperatively. We evaluated the response to touch sensation using the Semmes-Weinstein monofilaments test (SW test) and two-point discrimination (2PD), pain sensation, and temperature sensation. The right mental nerve did not respond to any quantitative test and sensation of pain just after the operation. One year and three months postoperatively, the SW value was 2.83 and 2PD distance was 11 mm, which were similar to the values on the normal side. The patient responded to sensations of heat and cold and 2-g pain sensation similar to that before the surgery. All responses to sensations were restored to normal one year and three months postoperatively. The postsurgical evaluation revealed marked improvement and significant recovery in sensations of the IAN, following immediate neurorrhaphy combined with PGA sheet during SSRO.

Background This study employed machine learning approaches to analyze sequences of adverse events (AEs) after left ventricular assist device (LVAD) implantation. Methods Data on patients implanted with the HeartWare HVAD durable LVAD were extracted from the ENDURANCE and ENDURANCE Supplemental clinical trials, with follow-up through 5 years. Major AEs included device malfunction, major bleeding, major infection, neurological dysfunction, renal dysfunction, respiratory dysfunction, and right heart failure (RHF). Time interval and transition probability analyses were performed. We created a Sankey diagram to visualize transitions between AEs. Hierarchical clustering was applied to dissimilarity matrices based on the longest common subsequence to identify clusters of patients with similar AE profiles. Results A total of 568 patients underwent HVAD implantation with 3590 AEs. Bleeding and RHF comprised the highest proportion of early AEs after surgery whereas infection and bleeding accounted for most AEs occurring after 3 months. The highest transition probabilities were observed with infection to infection (0.34), bleeding to bleeding (0.31), RHF to bleeding (0.31), RHF to infection (0.28), and bleeding to infection (0.26). Five distinct clusters of patients were generated, each with different patterns of time intervals between AEs, transition rates between AEs, and clinical outcomes. Conclusions Machine learning approaches allow for improved visualization and understanding of AE burden after LVAD implantation. Distinct patterns and relationships provide insights that may be important for quality improvement efforts.

Background Limited data are available on the role of direct oral anticoagulants (DOACs) for the treatment of upper extremities deep vein thrombosis (UEDVT). Objectives The aim of this study was to assess the effectiveness and safety of DOACs in the treatment of UEDVT. Methods Patients with an objectively confirmed acute UEDVT treated with DOACs were merged from prospective cohorts to a collaborative database. Primary study outcomes were recurrent venous thromboembolism (VTE) and major bleeding occurring during DOAC treatment. Results Overall, 188 patients were included in the study: mean age 52.4 ± 20.4 years, males 43.6%, patients with active cancer 29.2%. Twenty-nine percent of patients had 2 or more risk factors for VTE, 33.0% had catheter-related or pacemaker-related UEDVT. In 13.8% of patients, DOACs were started one month after UEDVT diagnosis or later. Active cancer was an independent predictor for delayed initiation of DOACs (OR 8.1, 95% CI 3.0–22.2). Mean duration of treatment with DOACs was 5.1 ± 2.8 months. During treatment with DOACs, recurrent VTE occurred in 0.9 per 100 patient-year, major bleeding in 1.7 and all-cause deaths in 6.0 per 100 patient-year. No fatal bleeding or fatal VTE recurrence were observed. During 232.1 patient-years of follow-up after DOAC withdrawal, recurrent VTE occurred in 3.0 per 100 patient-year. The 2019 ESC categories for risk of VTE recurrences were able to discriminate patient groups at different risk of events in the on and off-treatment periods. Conclusions Our data support the feasibility as well as the effectiveness and safety of DOACs for the treatment of acute UEDVT.

Bleeding remains a major source of morbidity associated with veno-venous extracorporeal membrane oxygenation (VV-ECMO). Moreover, there remains significant controversy, and a paucity of data regarding the ideal anticoagulation strategy for VV-ECMO patients. All patients undergoing isolated, peripheral VV-ECMO between January 2009 and December 2014 at our institution were retrospectively reviewed. Patients (n = 123) were stratified into one of three sequential eras of anticoagulation strategies: activated clotting time (ACT: 160-180 seconds, n = 53), high-partial thromboplastin time (H-PTT: 60-80 seconds, n = 25), and low-PTT (L-PTT: 45-55 seconds, n = 25) with high-flow (>4 L/min). Pre-ECMO APACHE II scores, SOFA scores, and Murray scores were not significantly different between the groups. Patients in the L-PTT group required less red blood cell units on ECMO than the ACT or H-PTT group (2.1 vs. 1.3 vs. 0.9; p < 0.001) and patients in the H-PTT and L-PTT group required less fresh frozen plasma than the ACT group (0.33 vs. 0 vs. 0; p = 0.006). Overall, major bleeding events were significantly lower in the L-PTT group than in the ACT and H-PTT groups. There was no difference in thrombotic events. In this single-institution experience, a L-PTT, high-flow strategy on VV-ECMO was associated with fewer bleeding and no difference in thrombotic events than an ACT or H-PTT strategy.

Background Patients with atrial fibrillation (AF) usually have a heterogeneous co‐morbid history, with dynamic changes in risk factors impacting on multiple adverse outcomes. We investigated a large prospective cohort of patients with multimorbidity, using a machine‐learning approach, accounting for the dynamic nature of comorbidity risks and incident AF. Methods Using machine‐learning, we studied a prospective US cohort using medical/pharmacy databases of 1 091 911 patients, with an incident AF cohort of 14 078 and non‐AF cohort of 1 077 833 enrolled in the 4‐year study. Five incident clinical outcomes (heart failure, stroke, myocardial infarction, major bleeding, and cognitive impairment) were examined in relationship to AF status (AF vs non‐AF), diverse multi‐morbid (conditions and medications) history, and demographic parameters (age and gender), with supervised machine‐learning techniques. Results Complex inter‐relationships of various comorbidities were uncovered for AF cases, leading to 6‐fold higher risk of heart failure relative to the non‐AF cohort (OR 6.02, 95% CI 5.72‐6.33), followed by myocardial infarction (OR=2.68), stroke (OR=2.19), and major bleeding (OR=1.36). Supervised machine learning algorithms on the original populations yielded comparable results for both neural network and logistic regression algorithms in terms of discriminant validity, with c‐indexes for incident adverse outcomes: heart failure (0.924, 95%CI 0.923‐0.925), stroke (0.871, 95%CI 0.869‐0.873), myocardial infarction (0.901, 95% CI 0.899‐0.903), major bleeding (0.700, 95%CI 0.697‐0.703), and cognitive impairment (0.919, 95% CI 0.9170.921). External calibration of all models demonstrated a good fit between the predicted probabilities and observed events. Decision curve analysis demonstrated that the obtained models were much more clinically useful than the “treat all” strategy. Conclusions Complex multimorbidity relationships uncovered using a machine learning approach for incident AF cases have major consequences for integrated care management, with implications for risk stratification and adverse clinical outcomes. This approach may facilitate automated approaches in the presence of multimorbidity, potentially helping decision making., External calibration for five predictive models (a – heart failure; b – stroke; c – myocardial infarction; d – major bleeding; e – cognitive impairment).

Objectives Using French transcatheter aortic valve replacement (TAVR) registries linked with the nationwide administrative databases, the study compared the rates of long-term mortality, bleeding, and ischemic events after TAVR in patients requiring oral anticoagulation with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs). Background The choice of optimal drug for anticoagulation after TAVR remains debated. Methods Data from the France-TAVI and FRANCE-2 registries were linked to the French national health single-payer claims database, from 2010 to 2017. Propensity score matching was used to reduce treatment-selection bias. Two primary endpoints were death from any cause (efficacy) and major bleeding (safety). Results A total of 24,581 patients who underwent TAVR were included and 8,962 (36.4%) were treated with OAC. Among anticoagulated patients, 2,180 (24.3%) were on DOACs. After propensity matching, at 3 years, mortality (hazard ratio [HR]: 1.37; 95% confidence interval [CI]: 1.12-1.67; P Conclusions In these large multicenter French TAVR registries with an exhaustive clinical follow-up, the long-term mortality and major bleeding were lower with DOACs than VKAs at discharge. The present study supports preferential use of DOACs rather than VKAs in patients requiring oral anticoagulation therapy after TAVR.

This review is devoted to the safety issues of anticoagulant therapy prescribed for the prevention of stroke and systemic embolism in patients with atrial fibrillation. Direct oral anticoagulants are considered worldwide in accordance with the guidelines for the diagnosis and treatment of atrial fibrillation as the preferred anticoagulant choice for the prevention of stroke and systemic embolism. Direct oral anticoagulants in comparison with vitamin K antagonists generally have similar efficacy, but different safety profiles, primarily, this concerns the risk of large extracranial and, primarily, gastrointestinal hemorrhages. To minimize the risk of bleeding during therapy with direct oral anticoagulants, an individual approach to the choice of the drug for each individual patient is required after assessing the risk of bleeding, searching for a potential bleeding substrate, correcting existing risk factors and eliminating, if possible, the substrate. When choosing an anticoagulant therapy, special attention should be paid to the most vulnerable categories of patients, such as patients of older age groups and patients with concomitant chronic kidney disease. Among the direct oral anticoagulants registered in the Russian Federation, according to meta-analyzes of key randomized clinical trials and real clinical trials, apixaban has the most optimal benefit: risk ratio in a wide range of patients, including vulnerable populations. Dynamic observation, including regular assessment of renal function, control of clinical blood analysis, erythrocyte and platelet levels, after prescribing an individually selected anticoagulant to the patient, ensures the maximum safety of therapy. Small, so-called, annoying bleeding is not a reason for canceling the anticoagulant, but requires a careful search for the causes of bleeding and their correction.

Aims: The net benefit of oral anticoagulants (OACs) in atrial fibrillation (AF) is poorly understood. We aimed to determine the NNT for net effect (NNT net) using calculator of absolute stroke risk (CARS) in anticoagulated patients with AF in real-world and clinical trial cohorts. Methods: Post-hoc analysis of patient-level data from the real-world Murcia AF Project and AMADEUS clinical trial. Baseline risk of stroke was determined using CARS. The risk of stroke and major bleeding events with OAC were determined using the number of respective events at 1-year. NNT net was calculated as a reciprocal of the net effect of absolute risk reduction with OAC (NNT net = 1/(absolute risk reduction of stroke[ARR stroke] − absolute risk increase of major bleeding[ARI bleeding])). Results: In total, 3511 patients were included (1306 [37.2%] real-world patients and 2205 [62.8%] clinical trial participants). The absolute 1-year stroke risk was similar across both cohorts. In the real-world cohort, OAC was associated with a 4.0% ARR stroke, 25 NNT benefit, 1.0% ARI bleeding, 100 NNT harm and 34 NNT net. In the clinical trial cohort, OAC was associated with a 3.8% ARR stroke, 27 NNT benefit, 1.6% ARI bleeding, 63 NNT harm and 46 NNT net. In both cohorts, the NNT net was significantly lower in patients with an excess stroke risk of ≥2% by CARS. Conclusion: Overall, the NNT net approach in AF incorporates information regarding baseline risk of stroke and major bleeding, and relative effects of OAC with the potential to include multiple additional outcomes and weighting of events based on their perceived effects by individual patients.

Background: The use of factor Xa inhibitors has grown in popularity; however, the risk of major bleeding events requires for the appropriate reversal agent. The recent approved agent for factor Xa inhibitor reversal, andexanet alfa, has limited clinical efficacy and safety data, and it can be a financial burden on healthcare systems due to its high cost. Four-factor prothrombin complex concentrate (4F-PCC) has been utilized off label in patients with factor Xa inhibitor-related bleedings. Objective: The aim of this study was to assess the safety and efficacy of 4F-PCC in managing factor Xa inhibitor-related bleedings. Methods: This is an observational, retrospective review of 4F-PCC usage in treating factor Xa inhibitor-related bleeds from May 2014 to December 2018 at a single health system. Efficacy was evaluated using the assessment criteria described by Sarode et al. Secondary outcomes analyzed included thromboembolic events, length of stay, mortality, and discharge disposition. Results: Fifty-nine patient charts were reviewed, and 48 patients were included in the study analysis. The administration of 4F-PCC achieved effective hemostasis in 33 patients (68%), and effective hemostasis was achieved in 12 patients (86%) who had intracranial hemorrhage and did not receive any surgical intervention. Thromboembolic events occurred in 4 patients within 30 days from 4F-PCC use. A majority of patients (85.4%) were discharged from the hospital to home or long-term care; 7 patients (14.6%) expired in the hospital. Conclusion: Efficacy was achieved in over half of the patient population in this cohort who received 4F-PCC for factor Xa inhibitor-related bleeding events.

Prolonged anticoagulation therapy is recommended for patients with intermediate-risk for recurrence of venous thromboembolism (VTE). The current study aimed to identify risk factors of VTE recurrence and major bleeding in intermediate-risk patients. The COMMAND VTE Registry is a multicenter registry enrolled consecutive 3027 patients with acute symptomatic VTE among 29 centers in Japan. The current study population consisted of 1703 patients with intermediate-risk for recurrence. The primary outcome measure was recurrent VTE during the entire follow-up period, and the secondary outcome measures were recurrent VTE and major bleeding during anticoagulation therapy. In the multivariable Cox regression model for recurrent VTE incorporating the status of anticoagulation therapy as a time-updated covariate, off-anticoagulation therapy was strongly associated with an increased risk for recurrent VTE (HR 9.42, 95% CI 5.97–14.86). During anticoagulation therapy, the independent risk factor for recurrent VTE was thrombophilia (HR 3.58, 95% CI 1.56–7.50), while the independent risk factors for major bleeding were age ≥ 75 years (HR 2.04, 95% CI 1.36–3.07), men (HR 1.52, 95% CI 1.02–2.27), history of major bleeding (HR 3.48, 95% CI 1.82–6.14) and thrombocytopenia (HR 3.73, 95% CI 2.04–6.37). Among VTE patients with intermediate-risk for recurrence, discontinuation of anticoagulation therapy was a very strong independent risk factor of recurrence during the entire follow-up period. The independent risk factors of recurrent VTE and those of major bleeding during anticoagulation therapy were different: thrombophilia for recurrent VTE, and advanced age, men, history of major bleeding, and thrombocytopenia for major bleeding. Unique identifier: UMIN000021132. COMMAND VTE Registry: http://www.umin.ac.jp/ctr/index.htm .

Scientific reports 11(1), 15172 (2021). doi:10.1038/s41598-021-94675-7, Published by Macmillan Publishers Limited, part of Springer Nature, [London]

To explore the novel treatment of small gastric submucosal tumors (SMTs) originating from the muscularis propria layer (SMT-MPs), we utilized endoscopic band ligation (EBL) with a precut of the covering mucosa.From Jan. 2012 to Dec. 2019, 111 patients with 124 gastric SMT-MPs were treated by precutting EBL. The clinical characteristics, operation duration, postoperative adverse events, and follow-up profiles were retrospectively collected.A total of 124 tumors from 111 patients were successfully treated by precutting EBL. No adverse events, including perforation and major bleeding, were observed. Furthermore, 93 patients (83.8%) underwent endoscopic surveillance postoperatively, and during the follow-up period, no local recurrence was detected.Precutting EBL appears to be a safe and simple method for removing gastric SMT-MPs16 mm (mainly indicated for potentially malignant GISTs), but further studies with longer follow-up are needed to assess the radicality of this intervention.

Coagulopathy and associated thrombotic complications are common conditions seen in COVID-19. Therefore, anticoagulants are an integral part of the treatment of patients with COVID-19.The aim of the study was to compare the efficacy of oral anticoagulants and low molecular weight heparins in the prevention of pulmonary embolism and their safety in terms of major bleeding incidence, as well as to evaluate the cost-effectiveness of using oral anticoagulants in the treatment of COVID-19.Materials and methods. Two stages of patient management were compared: before and after the start of a widespread use of oral anticoagulants (OAC). The incidence of pulmonary embolism and gastrointestinal bleeding during the compared time periods was analyzed to assess the efficacy and safety of anticoagulants. To assess the cost-effectiveness, we compared the cost of anticoagulants per day of treatment and per patient.Results. The incidence of pulmonary embolism and gastrointestinal bleeding did not differ during the compared time periods. Despite the increased frequency of anticoagulant use, the costs per day of treatment and per patient decreased after the start of a widespread use of OACs.Conclusion. According to the results of the study, inclusion of OACs in COVID-19 management protocols allows to reduce treatment costs without compromising its efficacy and safety. However, the short period of comparison does not allow drawing any firm conclusions. Additional large-scale comparative studies are needed.

Direct oral anticoagulants (DOACs) are being increasingly used in patients with chronic thromboembolic hypertension (CTEPH), however, the data on their safety and efficacy are scarce and contradictory. We systematically searched MEDLINE and Google Scholar databases from January 2010 to January 2021 for studies of DOACs in CTEPH. Three observational studies, 2 abstracts and one case series met our inclusion criteria. While these studies reported similar or even less rates of major bleeding in patients receiving DOACs compared with vitamin K antagonists, there were concerns about the possibility of increased risk of venous thromboembolism recurrence with DOAC therapy. Further studies are warranted to better define the role of DOACs in CTEPH.

Background Patients with baseline thrombocytopenia can have increased mortality and morbidity, but are typically excluded from randomized clinical trials studying acute coronary syndromes (ACS). We sought to better define the effect thrombocytopenia on clinical outcomes in ACS patients. Methods Patients identified from the NCDR Chest Pain registry at Mayo Clinic Arizona from Oct 2015 to Sep 2018 were retrospectively classified into two groups: TP (platelet Results Five hundred and thirty-six patients were identified, and 72 patients (13%) had thrombocytopenia. The median follow-up time was 1.1 years. The TP group was older (TP vs. control: mean age 73 ± 13 years vs. 70 ± 13 years; P = 0.026). In patients discharged on dual-antiplatelet therapy, the TP group had higher all-cause mortality (23% vs. 7.3%; P = 0.007) but not major bleeding events (11% vs. 5.0%; P = 0.123). Only all-cause mortality increased with the severity of thrombocytopenia (TPmod vs. TPmild vs. control: 33% vs. 24% vs. 7.3%; P = 0.007). Conclusions In patients with ACS, baseline thrombocytopenia is associated with increased all-cause mortality and all bleeding events without net MACE benefit. Further study is needed to identify the optimal antiplatelet strategy in this higher risk population.

BACKGROUND The aim of this study is to evaluate clinical outcomes after percutaneous coronary intervention (PCI) in patients with cancer.Methods and Results:Cancer screening was recommended before PCI in consecutive 1,303 patients who underwent their first PCI. By using cancer screening, cancer was diagnosed in 29 patients (2.2%). In total, 185 patients had present or a history of cancer. Patients with cancer more often suffered from non-cardiac death than those without (4.4% vs. 1.5%, P=0.006), and patients with cancer requiring ongoing therapy (n=18) more often suffered from major bleeding compared with those with recently (≤12 months) diagnosed cancer who do not have ongoing therapy (n=59) (16.7% vs. 3.4%, P=0.049). During the 1-year follow up, 25 patients (2.0%) were diagnosed as having cancer, in which 48.0% of bleeding events led to a cancer diagnosis. Patients with high bleeding risk according to the Academic Research Consortium for high bleeding risk (ARC-HBR) were associated with a greater 1-year major bleeding risk than those without high bleeding risk in patients with (7.9% vs. 0.0%, P=0.02) and without cancer (7.1% vs. 2.5%, P

The change in practice of transcatheter aortic valve replacement (TAVR) to a minimalist approach is a debate. Online database search for studies that compared the minimalist approach with the standard approach for TAVR were searched from inception through September 2020. We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) using the fixed or random-effects model. A total of 9 studies with 2,880 TAVR patients (minimalist TAVR;1066 and standard TAVR; 1,814) were included. Compared to standard approach, there were no significant differences in in-hospital mortality, 30-day mortality, or hospital readmissions. However, there was a reduced risk of acute kidney injury (OR0.49;95%CI0.27���0.89), major bleeding (OR0.21;95%CI0.12���0.38) and major vascular complications (OR0.60,95%CI0.39���0.91) associated with the minimalist TAVR group. There was comparatively shorter hospital length of stay (mean difference ���2.41;95%CI-2.99,-1.83) days, procedural time (mean difference ���43.99;95%CI-67.25,-20.75) minutes, fluoroscopy time (mean difference ���2.69;95%CI-3.44,-1.94) minutes and contrast volume (mean difference ���26.98;95%CI-42.18,-11.79) ml in the minimalist TAVR group. This meta-analysis demonstrated potential benefits of the minimalist TAVR approach over the standard approach regarding some adverse clinical outcomes as well as procedural outcomes without significant differences in mortality or readmission rates.

PURPOSE: To systematically review available evidence of indirect comparisons from RCTs and direct comparisons from observational studies regarding the comparative effectiveness and safety of DOACs in patients with AF.METHODS: Electronic databases including EMBASE, MEDLINE, and PUBMED were searched up to June 5th, 2020. Primary endpoints included effectiveness (stroke or systemic embolism [SE]) and safety (major bleeding) outcomes. Bucher methods and random-effects models were conducted for indirect and direct comparisons among DOACs, respectively. Ranking probability analyses and the number needed to treat for net effect (NNTnet) were applied.RESULTS: A total of 36 studies, involving 7 RCTs (n = 60,292 patients) and 29 observational studies (n = 1,164,821 patients), were included for analyses. Regarding the risk of stroke/SE, no significant differences were found from indirect comparisons of RCTs among the DOACs. For major bleeding, apixaban tended to be safer than rivaroxaban and dabigatran based on both direct and indirect comparisons (all p CONCLUSIONS: Apixaban appeared to have a favorable effectiveness-safety profile compared with the other DOACs in AF for stroke prevention, based on evidence from both direct and indirect comparisons. However, additional high-quality evidence is needed to support firm recommendations on clinical decision-making.

Background: The effectiveness and safety of non-heparin anticoagulants for the treatment of heparin-induced thrombocytopenia (HIT) are not fully established, and the optimal treatment strategy is unknown. In a systematic review and meta-analysis, we aimed to determine precise rates of platelet recovery, new or progressive thromboembolism (TE), major bleeding, and death for all non-heparin anticoagulants and to study potential sources of variability. Methods: Following a detailed protocol (PROSPERO: CRD42020219027), EMBASE and Medline were searched for all studies reporting clinical outcomes of patients treated with non-heparin anticoagulants (argatroban, danaparoid, fondaparinux, direct oral anticoagulants [DOAC], bivalirudin, and other hirudins) for acute HIT. Proportions of patients with the outcomes of interest were pooled using a random-effects model for each drug. The influence of the patient population, the diagnostic test used, the study design, and the type of article was assessed. Findings: Out of 3’194 articles screened, 92 studies with 119 treatment groups describing 4’698 patients were included. The pooled rates of platelet recovery ranged from 74% (bivalirudin) to 99% (fondaparinux), TE from 1% (fondaparinux) to 7% (danaparoid), major bleeding from 1% (DOAC) to 14% (bivalirudin), and death from 7% (fondaparinux) to 19% (bivalirudin). Confidence intervals were mostly overlapping, and results were not influenced by patient population, diagnostic test used, study design, or type of article. Interpretation: Effectiveness and safety outcomes were similar among various anticoagulants, and significant factors affecting these outcomes were not identified. These findings support fondaparinux and DOACs as viable alternatives to conventional anticoagulants for treatment of acute HIT in clinical practice. Registration Information: PROSPERO: CRD42020219027. Funding Information: This study was supported by a research grant of the Swiss National Science Foundation (#179334). Declaration of Interests: Conflict-of-interest disclosure: M.N. received research grants from Bayer Healthcare. A.C. has served as a consultant for synergy and his institution has received research support on his behalf from alexion, Bayer, Novartis, novo Nordisk, Pfizer, Sanofi, spark, and Takeda. All other authors declare that no conflict of interest exists.

Venous thromboembolism (VTE) is a known cause of morbidity and mortality, especially among acutely ill medical patients. Although VTE prophylaxis is part of post-discharge clinical care in surgical patients, there is controversy regarding its use in acutely ill medical patients and the current guideline statements suggest against its routine use. Recent clinical trials (APEX, MAGELLAN and MARINER) compared the safety and efficacy of direct oral anticoagulants (including betrixaban and rivaroxaban) with the standard of the care, enoxaparin, to identify the risk–benefit tradeoff. In this review, we summarized the key findings from these trials and substudies and recent updates in society guidelines regarding VTE prevention. In addition, we discussed the potential barriers, cost-effectiveness, and COVID-19 with respect to the implementation of extended-duration or post-discharge usage of direct oral anticoagulants.

Background Meta-analyses are widely used to strengthen available evidence and obtain more precise estimates of treatment effect than any individual trial. Paradoxically, multiplication of meta-analyses on the same topic can lead to confusion as practitioners no longer benefit from a rapid and synthetic response. This phenomenon may appear disproportionate when the number of published meta-analyses exceeds the number of original studies. Objectives To describe an example of redundant meta-analyses published in the same area with the same randomized clinical trials (RCTs). Methods A systematic review was performed to identify all published meta-analyses of original RCTs that compared direct oral anticoagulants with low molecular weight heparins in cancer patients with venous thromboembolism (VTE). Forest plots were used to represent the meta-analyses results for efficacy (VTE recurrence) and safety (major bleeding) endpoints. An authors' network was constructed to explore the links between the authors of the published meta-analyses. Results In the past 3 years, four original RCTs were the subject of 20 published meta-analyses by 142 authors: five, four, and 11 meta-analyses pooled the data of two, three, and four RCTs, respectively. The results of meta-analyses were similar regarding the risks of VTE recurrence and major bleeding. The 11 meta-analyses of four RCTs were published within 6 months of the publication of the last RCT. Conclusions The epidemic proportions of such redundant literature and authorship could be moderated by developing "living" meta-analyses and encouraging authors of new RCTs to update the corresponding meta-analysis in the same paper as their original research.

Background: Whether concomitant administration of anticancer agents influences the efficacy and safety of oral anticoagulants in patients treated for cancer-associated venous thromboembolism (VTE) is undefined. The pharmacological interaction between anticancer agents and direct oral anticoagulants is perceived as a concern.Methods: We evaluated the effects of concomitant administration of anticancer agents on recurrent VTE, major bleeding and death in patients with cancer-associated VTE randomised to receive apixaban or dalteparin in the Caravaggio study.Results: Anticancer agents were concomitantly given to 336 patients (58.3%) treated with apixaban and to 332 patients (57.3%) treated with dalteparin. In patients treated with apixaban, recurrent VTE occurred in 20 (6.0%) and 12 (5.0%) among patients treated or not treated with anticancer agents, respectively (hazard ratio [HR] = 1.14; 0.55-2.38); major bleeding occurred in 12 (3.6%) and 10 (4.2%) patients , respectively (HR = 0.79; 0.34-1.82), and death occurred in 74 (22.0%) and 61 (25.4%) patients , respectively (HR = 0.71; 0.51-1. 00). In patients treated with dalteparin, recurrent VTE occurred in 24 (7.2%) and 22 (8.9%) among patients treated or not treated with anticancer agents, respectively (HR = 0.71; 0.40-1.28); major bleeding occurred in 16 (4.8%) and 7 (2.8%) patients, respectively (HR = 1.78; 0.66-4.79 ), and death occurred in 87 (26.2% ) and 66 (26.7 %) patients, respectively (HR = 0.85; 0.62-1.18). The comparative efficacy and safety of apixaban and dalteparin was not different in patients treated or not treated with anticancer agents. No effect on recurrent VTE, major bleeding or death was observed with inhibitors or inducers of P-glycoprotein and/or CYP3A4.Conclusion: In our study, concomitant administration of anticancer agents had no effect on the risk of VTE recurrence or major bleeding in patients treated with apixaban or dalteparin for cancer-associated VTE.(c) 2021 Elsevier Ltd. All rights reserved.

Background A factor XIII (FXIII) level >30% is considered necessary to prevent spontaneous bleeding. Bleeding is also a risk in patients with acquired FXIII deficiency, but the hemostatic level of FXIII in this context remains to be determined. Methods We retrospectively analyzed all patients diagnosed with acquired FXIII deficiency at a large hospital over 3 years (study ID NCT04416594, http://www.clinicaltrials.gov) and assessed clinical data to identify the best cut-off point for FXIII activity to distinguish between low and high risk of major bleeding in a mixed medical and surgical population. Results Of the 97 patients who experienced bleeding despite a normal coagulation test, 43.2% had FXIII activity Conclusion Acquired FXIII deficiency is associated with high morbidity. The hemostatic level of FXIII in the setting of acquired FXIII deficiency might be above 30%.