Reduce Bleeding Complications Research Articles

Emicizumab, a humanized bispecific antibody to coagulation factors IXa and X with a factor VIIIa-cofactor activity.

Hemophilia A is a congenital disorder caused by deficiency or malfunction of coagulation factor (F) VIII. While exogenously provided FVIII effectively reduces bleeding complications in many hemophilia A patients, multiple efforts are underway to develop new drugs to meet the needs that conventional FVIII agents do not. We have been long engaged in creating and clinically developing a humanized anti-FIXa/FX asymmetric bispecific IgG antibody with a FVIIIa-cofactor activity. Since this project was born from a creative and unique idea, our group recognized from the first that it would face many difficulties in the course of research including establishment of industrial manufacturability of an asymmetric bispecific IgG antibody. The group actually faced various challenges, but addressed all of them during about 10years of research, and successfully created the potent humanized bispecific antibody, emicizumab. Emicizumab has showed clinical benefits in the human trials among which the first one was started in 2012, and has been currently approved in US, EU, Japan, and some other countries. It is now expected to improve the quality of life of patients and their families. In this article, we review the course of the research and clinical development of emicizumab, and describe its molecular characteristics.

Interrupted versus uninterrupted novel oral anticoagulant peri-implantation of cardiac device: A single-center randomized prospective pilot trial.

Many patients requiring cardiac implantable electronic device (CIED) implantation are on long-term oral anticoagulant therapy. While continuation of warfarin has been shown to be safe and reduce bleeding complications compared to interruption of warfarin therapy and heparin bridging, it is not known which novel oral anticoagulants (NOAC) regimen (interrupted vs uninterrupted) is better in this setting. One-hundred and one patients were randomized to receive CIED implantation with either interrupted or uninterrupted/continuous NOAC therapy before surgery. No heparin was used in either treatment arm. The primary end-point was the presence of a clinically significant pocket hematoma after CIED implantation. The secondary end-point was a composite of other major bleeding events, device-related infection, thrombotic events, and device-related admission length postdevice implantation. Both treatment groups were equally balanced for baseline variables and concomitant medications. One clinically significant pocket hematoma occurred in the uninterrupted NOAC group and none in the interrupted group (P=0.320). There was no difference in other bleeding complications. No thrombotic events were observed in either of the two groups. Despite the paucity of bleeding events, data from this pilot study suggest that uninterrupted NOAC therapy for CIED implantation appears to be as safe as NOAC interruption and does not increase bleeding complications.

Recommendations for the post-operative management of an existing Warfarin therapy after lower limb joint arthroplasty

BackgroundWarfarin administration after lower limb joint replacements is associated with a high bleeding risk, creating the circumstances for periprosthetic joint infections, increased treatment costs and prolonged Length of Stay (L.o.S). We believe that previously warfarinized patients can be treated safely and discharged without delays, if appropriate policies are established and adhered to. MethodsThis is a retrospective cohort study. We have collected and analyzed data from an audit cycle between 2012 and 2015 on: 1) the post-operative Warfarin reloading protocol, identifying 4 distinct patterns: usual dose, 1.5 times or double the usual dose for 2 days and overloading, 2) timing of reloading: Evening of Surgery vs post-op Day 1, 3) frequency of INR testing: daily vs intermittent, 4) time required to reach a therapeutic INR value ≥2.0, 5) rate of INR variations ≥4.0 and 6) bleeding complications, 7) and the overall L.o.S. ResultsWe found a significant difference in the time required to reach an INR ≥2.0 between reloading with the usual dose and all other protocols (p < 0.001) without abolishing adverse sequelae. Daily INR testing reduced bleeding complications and INR variations at a significant (p < 0.001) and non-significant level respectively, while timing of restarting showed no significant effect. We found a correlation between INR variations and bleeding complications (odds ratio: 4.65, C.I: 0.59–30.87). 41% of the cohort was discharged on the day their INR turned therapeutic with an average L.o.S of 6.5 days. ConclusionWe recommend to: 1) restart Warfarin at double (or in exceptional cases 1.5 times) the patient's maintenance dose for the first two doses, 2) starting on the Evening of Surgery, 3) with daily INR monitoring after the second loading dose, 4) using point of care testing devices, 5) and dosing thereafter to be guided by an anticoagulation service or computer assistance.

TCT-846 Multicenter Study of the Efficacy and Safety of Distal Radial Approach in Coronary Angiography and Intervention

The transradial access for coronary angiography and intervention has advantages in increased safety and patient comfort with reduction of bleeding complications and early ambulation when compared with the transfemoral access. The distal transradial approach (dTRA), a newly developed technique, is

P1905Figure-of-eight stitch access site closure significantly reduces bleeding complications in patients undergoing cryoballoon ablation guided by intracardiac echocardiography

P1905Figure-of-eight stitch access site closure significantly reduces bleeding complications in patients undergoing cryoballoon ablation guided by intracardiac echocardiography

Strategies to increase the use of forearm approach during coronary angiography and interventions.

The aim of this article is to focus on the utilization of forearm approach for cardiac catheterization in challenging groups of patients. Radial and ulnar approaches have gained significant popularity among the majority of interventional cardiologists. Multiple studies have demonstrated the feasibility, safety and efficacy of forearm route for cardiac catheterization and have highlighted the significant reduction in bleeding complications by avoiding the puncture of the groin. In this review we present the strategies need to be followed in order to apply the forearm approach in challenging group of patients.

Hereditary hemorrhagic telangiectasia: diagnosis and management from the hematologist's perspective.

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is an autosomal dominant disorder that causes abnormal blood vessel formation. The diagnosis of hereditary hemorrhagic telangiectasia is clinical, based on the Curaçao criteria. Genetic mutations that have been identified include ENG, ACVRL1/ALK1, and MADH4/SMAD4, among others. Patients with HHT may have telangiectasias and arteriovenous malformations in various organs and suffer from many complications including bleeding, anemia, iron deficiency, and high-output heart failure. Families with the same mutation exhibit considerable phenotypic variation. Optimal treatment is best delivered via a multidisciplinary approach with appropriate diagnosis, screening and local and/or systemic management of lesions. Anti-angiogenic agents such as bevacizumab have emerged as a promising systemic therapy in reducing bleeding complications but are not curative. Other pharmacological agents include iron supplementation, antifibrinolytics and hormonal treatment. This review discusses the biology of HHT, management issues that face the practising hematologist, and considerations of future directions in HHT treatment.

Antithrombotic therapy in patients with non-valvular atrial fibrillation undergoing percutaneous coronary intervention: should we change our practice after the PIONEER AF-PCI and RE-DUAL PCI trials?

The number of patients with atrial fibrillation undergoing percutaneous coronary intervention (PCI) is increasing. Since these patients have a CHA2DS2-VASc score of 1 or higher, they should be treated with oral anticoagulation to prevent stroke. However, combination therapy with oral anticoagulation for prevention of embolic stroke and dual platelet inhibition for prevention of coronary thrombosis significantly increases bleeding complications. The optimal combination, intensity and duration of antithrombotic combination therapy is still not known. In the rather small randomized WOEST trial, the combination of a vitamin K antagonist (VKA) and clopidogrel decreased bleeding compared to the conventional triple therapy with VKA, clopidogrel and aspirin. In the PIONEER AF-PCI trial, two rivaroxaban-based treatment regimens significantly reduced bleeding complications compared to conventional triple therapy without increasing embolic or ischemic complications following PCI. Dual therapy with rivaroxaban and clopidogrel appeared to provide an optimal risk-benefit ratio. In the RE-DUAL PCI trial, dual therapy with dabigatran also reduced bleeding complications compared to conventional triple therapy. With respect to the composite efficacy end point of thromboembolic events (myocardial infarction, stroke, or systemic embolism), death, or unplanned revascularization dabigatran-based dual therapy was non-inferior to VKA-based triple therapy. The upcoming trials AUGUSTUS with apixaban and ENTRUST-PCI with edoxaban will further examine the use of NOACs in this setting. While recent guidelines recommend NOAC-based dual therapy in only a subset of patients (those who are at increased risk of bleeding), the available data now suggest that this should be the preferred choice for the majority of patients. Adding aspirin to this primary choice for up to 4weeks in patients at especially high ischemic risk would likely prevent atherothrombotic events, but this needs further investigation. Taken together, it is time to adjust our practice and move to dual therapy consisting of a NOAC plus clopidogrel in most patients.

Dual antiplatelet therapy after percutaneous left atrial appendage occlusion: single center experience with the Amplatzer Cardiac Plug

Background: Percutaneous left atrial appendage occlusion (LAAO) is an alternative to anticoagulation in atrial fibrillation patients at high bleeding risk. Dual antiplatelet therapy (DAPT) is generally recommended in the months following the procedure to prevent thrombotic complications. The aim of this study was to evaluate the safety and efficacy of DAPT after LAAO in a single-centre population of high bleeding risk patients.Methods: All patients who received DAPT after LAAO using the Amplatzer Cardiac Plug at Jessa Hospital (Hasselt, BE) between February 2011 and October 2016 were included. Patient characteristics, procedural outcome and clinical events (bleeding, stroke and adverse events) were prospectively followed. Changes in antithrombotic and/or anticoagulant regimens were assessed.Results: Thirty-nine patients (77 ± 7 years, 51% male, CHA2DS2-VASc 5(3–6), Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly (HAS-BLED) 3(3–4)) were included. An initial strategy of one month DAPT (n = 2) was changed to six months DAPT (n = 37) after one thrombotic complication (device thrombosis) at 4.5 months. Post-procedural DAPT duration was 6.1 ± 3.7 months, after which aspirin monotherapy (62%), no antiplatelet/anticoagulant therapy (15%) or a tailored antithrombotic regimen was maintained. At mean follow-up of 21 ± 13 months, seven patients had died (18%), no strokes had occurred (0%) and nine bleedings of which four were major (10%). All major bleedings occurred within the first six months after the procedure during DAPT.Conclusion: Antithrombotic therapy after percutaneous LAAO is needed to prevent thrombotic complications, yet these impose bleeding complications in this high-risk population. Further efforts are needed to define the optimal duration of DAPT, aimed at reducing bleeding complications while maintaining a low thrombosis rate.

Bivalirudin or Heparin in Patients Undergoing Invasive Management of Acute Coronary Syndromes

BackgroundContrasting evidence exists on the comparative efficacy and safety of bivalirudin and unfractionated heparin (UFH) in relation to the planned use of glycoprotein IIb/IIIa inhibitors (GPIs). ObjectivesThis study assessed the efficacy and safety of bivalirudin compared with UFH with or without GPIs in patients with acute coronary syndrome (ACS) who underwent invasive management. MethodsIn the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX) program, 7,213 patients were randomly assigned to receive either bivalirudin or UFH with or without GPIs at discretion of the operator. The 30-day coprimary outcomes were major adverse cardiovascular events (MACEs) (a composite of death, myocardial infarction, or stroke), and net adverse clinical events (NACEs) (a composite of MACEs or major bleeding). ResultsAmong 3,603 patients assigned to receive UFH, 781 (21.7%) underwent planned treatment with GPI before coronary intervention. Bailout use of GPIs was similar between the bivalirudin and UFH groups (4.5% and 5.4%) (p = 0.11). At 30 days, the 2 coprimary endpoints of MACEs and NACEs, as well as individual endpoints of mortality, myocardial infarction, stent thrombosis or stroke did not differ among the 3 groups after adjustment. Compared with the UFH and UFH+GPI groups, bivalirudin reduced bleeding, mainly the most severe bleeds, including fatal and nonaccess site−related events, as well as transfusion rates and the need for surgical access site repair. These findings were not influenced by the administered intraprocedural dose of UFH and were confirmed at multiple sensitivity analyses, including the randomly allocated access site. ConclusionsIn patients with ACS, the rates of MACEs and NACEs were not significantly lower with bivalirudin than with UFH, irrespective of planned GPI use. However, bivalirudin significantly reduced bleeding complications, mainly those not related to access site, irrespective of planned use of GPIs. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX [MATRIX]; NCT01433627)

Impact of diabetes on benefit of switching dual antiplatelet therapy after acute coronary syndrome: A subanalysis of the TOPIC randomized study

The TOPIC trial showed that switching dual antiplatelet (DAPT) from aspirin plus a newer P2Y12 blocker (prasugrel or ticagrelor) to aspirin plus clopidogrel led to a reduction in bleeding complications with similar risk of ischemic recurrence. The objective of this analysis was to evaluate the impact of diabetes on the benefit of switched strategy. TOPIC study randomized patients admitted for an ACS without adverse event at 1 month on aspirin and a newer P2Y12 blocker, to aspirin and clopidogrel (switched DAPT) or continuation of their drug regimen (unchanged DAPT). Three hundred and twenty-two patients were randomized to switched DAPT and 323 to unchanged DAPT. The primary endpoint of this analysis aimed to evaluate the impact of diabetes on clinical outcomes (composite of cardiovascular death, urgent revascularization, stroke and bleeding BARC classification ≥ 2) at 1 year. Hundred and seventy-seven patients were diabetics corresponding to 84 (26%) in the switched arm and 93 (29%) in the unchanged. No differences in primary outcome incidence was observed in the unchanged arm between diabetic and non-diabetic (25.8% vs. 26.5%, HR 95% CI 0.96 (0.60–1.54), P = 0.88) while in the switched arm, primary endpoint occurred significantly more in diabetics (22.6% vs. 10.1%, 95% CI 2.72 (1.37–5.42), P < 0.01). Benefit of switched strategy was maintained in non-diabetic patients (HR 95% CI 0.37 (0.34–0.56), P < 0.01) while no significant differences were observed in diabetic patients (HR 95% CI 0.83 (0.45–1.50), P = 0.53). This lack of benefit in the diabetic arm was related to increased risk of recurrent ischemic events (HR 95% CI 1.52 (0.70–3.27), P = 0.29) ( Fig. 1 ) despite reduction in bleedings BARC ≥ 2 (HR 0.37, P = 0.04) ( Fig. 1 ). Switching DAPT proved its benefit after ACS in terms of bleeding prevention. However, in diabetic patients switching DAPT was associated with excess of ischemic events despite bleeding prevention. Switching DAPT strategy should be preferred in non-diabetic patients.

Benefit of switching dual antiplatelet therapy after ACS on dual antiplatelet therapy adherence: A prespecified analysis of the TOPIC randomized study

The Timing Of Platelet Inhibition after acute Coronary Syndrome (TOPIC) trial showed that switching dual antiplatelet (DAPT) from aspirin plus a newer P2Y12 blocker (prasugrel or ticagrelor) to aspirin plus clopidogrel 1 month after an acute coronary syndrome (ACS) led to a reduction in bleeding complications with similar risk of ischemic recurrence. The objective of this prespecified analysis was to evaluate the impact of switching strategy on DAPT adherence. TOPIC study randomized patients admitted for an ACS without adverse event at 1 month on aspirin and a newer P2Y12 blocker, to aspirin and clopidogrel (switched DAPT) or continuation of their drug regimen (unchanged DAPT). Medical adherence to prescribed DAPT was assessed at 6 months and 1 year. Six hundred and forty-six patients were randomized and 645 analyzed, corresponding to 322 patients in the switched DAPT and 323 in the unchanged DAPT group. At 6 months and 1 year, the allocated DAPT regimen was significantly used more often in the switched group than in the unchanged DAPT group: 298 (92.5%) vs. 264 (81.7%) ( P < 0.01) at 6 months and 277 (87.7%) vs. and 242 (76.1%) ( P < 0.01) at 1 year. The reason for DAPT change was related to an adverse event in 66% of cases corresponding to an ischemic event in 17 patients (14.8%) and bleeding in 59 patients (51.3%) ( Fig. 1 ). In multivariable analysis, unchanged DAPT strategy and ischemic or bleeding events were significantly associated with non-adherence to prescribed DAPT ( Table 1 ). A switched DAPT was associated with significant improvement in the number of patients on prescribed DAPT at 6 months and 1 year following ACS. This improved adherence was related to reduction of side effects.

Non-vitamin K Antagonist Oral Anticoagulant After Acute Coronary Syndrome: Is There a Role?

Despite dual antiplatelet therapy (DAPT) including potent P2Y12 inhibitors, recurrent ischaemic events occur in a significant number of patients after acute coronary syndrome (ACS), warranting new antithrombotic strategies. Combinations of non-vitamin K antagonist oral anticoagulant (NOAC) with antiplatelet therapy have been tested in several large phases II and III randomised trials. Overall, current evidence suggests that the use of NOACs on top of DAPT after ACS reduces the rate of recurrent ischaemic events, albeit at the price of increased risk for major bleeding. In the particular field of patients with ACS and atrial fibrillation, NOACs may be associated with reduced bleeding complications compared with vitamin K antagonist. Further randomised trials evaluating low-dose NOAC combined with single antiplatelet therapy are warranted.

A Nursing-Led Examination of Radial Artery Diameters, Occlusion Rates and Vascular Complications Utilising Ultrasound Measurements

Background: Transradial access is increasingly common for cardiac catheterisation. Benefits of this approach include reduced bleeding complications, length of hospital stay, and costs for the institution.

Thoracentesis in advanced cancer patients with severe thrombocytopenia: Ultrasound guide improves safety and reduces bleeding risk.

Patients with severe thrombocytopenia are considered at risk for bleeding during invasive procedures as thoracentesis. The use of ultrasound (US) significantly reduces the rate of pneumothorax from thoracentesis, but there is a lack of data on safety and efficacy of US guidance in reducing bleeding complications in thoracentesis performed on patients with severe thrombocytopenia. We retrospectively analysed the efficacy and safety of thoracentesis in cancer patients with severe thrombocytopenia. From January 2005 to December 2011, 462 patients underwent thoracentesis. Procedures were divided into 2 groups: performed without or with US guidance. All procedures were evaluated for bleeding complications as defined by the National Institutes of Health Common Terminology Criteria for Adverse Events. A total of 436 consecutive evaluable thoracentesis were analysed. Thoracentesis was performed with US guidance in 310 cases. Forty-one patients (9.40%) had severe thrombocytopenia. In 32 of these 41 patients, thoracentesis was performed under US guidance while in 9 cases the procedure was performed without US guidance. Three mild haemorrhagic complications (0.69% of the procedures performed) were observed and all occurred in group of the 9 (33.33%) patients with severe thrombocytopenia who underwent thoracentesis without US guidance. No haemorrhagic complications were recorded in the 427 patients, including the 32 patients with severe thrombocytopenia, in whom thoracentesis was performed with US guidance. US guided thoracentesis is a safe and effective approach in cancer patients with severe thrombocytopenia. Our results indicate that this procedure, when US-guided, can be safety performed even in patients with platelet count below 30 × 109 /L.

Enhancing Outcomes for Outpatient Percutaneous Coronary Interventions.

Purpose and Objectives:A quality improvement project was conducted to create a sustainable continuum of care for increased volumes of outpatients receiving percutaneous coronary interventions. Dramatic growth exposed system vulnerabilities and left staff overwhelmed. Four postinterventional project objectives included reducing preprocedural preparation times, reducing bleeding complications, reducing hospital length of stay, and collectively increasing patient satisfaction.Description of the Project:Amidst creating a specialized postintervention coronary recovery area and acquiring and training existing preregistration and recovery nurses, a fragmented system of care was united. The clinical nurse specialist–led project used a systematic and evidence-based implementation process to harmoniously acclimate perioperative staff. An evaluation process further defined new opportunities to support a growing service line.Outcomes:Postimplementation data were collected over a 3-month period. An overall improvement was found in all targeted objectives, despite an upsurge in case volumes. A moderately significant correlation (r [105] = 0.424, P < .001) was found between bleeding occurrences and hospital length of stay.Conclusion:The synergy between interdepartmental collaboration and strategic staffing reallocation was shown to be invaluable to alleviate procedural areas of service, such as the cardiac catheterization laboratory. As a project champion, the clinical nurse specialist is an essential catalyst to identify and creatively surmount system-level challenges.

TCT-90 HAS-BLED Score and Other Predictors of Bleeding in Catheter-Directed Thrombolysis for Pulmonary Embolism

Catheter-directed thrombolysis (CDT) in the treatment of acute pulmonary embolism (PE) aims to reduce bleeding complications while maintaining efficacy compared to systemic fibrinolysis. While studies have shown CDT to have superior hemodynamic outcomes compared to systemic anticoagulation alone,

Incorporating Comprehensive Management of Direct Oral Anticoagulants into Anticoagulation Clinics.

Anticoagulation clinics emerged as a means to optimize warfarin effectiveness and minimize bleeding risks. Anticoagulation clinics have traditionally been warfarin-based models due to the need for frequent blood-level monitoring, drug interactions, dietary considerations, and periprocedural management with warfarin. These models have demonstrated improved anticoagulation control and reduced bleeding complications for patients taking warfarin. Direct oral anticoagulants (DOACs) emerged with the perception of improved convenience due to the lack of blood-level monitoring and lack of dietary considerations. Despite the advantages of DOAC therapy, new challenges exist with their management, warranting ongoing monitoring. Such challenges include prescribing and dosing issues, drug adherence, drug interactions, and high drug cost. Comprehensive anticoagulation centers are needed to manage and monitor all oral anticoagulants including DOACs. The objectives of this review are to describe the challenges and opportunities that exist in the management of DOACs and to describe a practice model that integrates a DOAC management service into the traditional anticoagulation clinic.

Renal replacement therapy and anticoagulation.

Today, up to 20% of all intensive care unit patients require renal replacement therapy (RRT), and continuous renal replacement therapies (CRRT) are the preferred technique. In CRRT, effective anticoagulation of the extracorporeal circuit is mandatory to prevent clotting of the circuit or filter and to maintain filter performance. At present, a variety of systemic and regional anticoagulation modes for CRRT are available. Worldwide, unfractionated heparin is the most widely used anticoagulant. All systemic techniques are associated with significant adverse effects. Most important are bleeding complications and heparin-induced thrombocytopenia (HIT-II). Regional citrate anticoagulation (RCA) is a safe and effective technique. Compared to systemic anticoagulation, RCA prolongs filter running times, reduces bleeding complications, allows effective control of acid-base status, and reduces adverse events like HIT-II. In this review, we will discuss systemic and regional anticoagulation techniques for CRRT including anticoagulation for patients with HIT-II. Today, RCA can be recommended as the therapy of choice for the majority of critically ill patients requiring CRRT.

Transradial versus transfemoral intervention in ST-segment elevation myocardial infarction patients in Korean population.

Background/AimsTransradial intervention (TRI) is becoming the preferred method over transfemoral intervention (TFI) because TRI is associated with lower incidence of major bleeding and vascular complications. However, there has been limited published data regarding the clinical outcomes of TRI versus TFI in Korean patients with ST-elevation myocardial infarction (STEMI).MethodsA total of 689 consecutive STEMI patients who underwent primary percutaneous coronary intervention (PCI) with drug-eluting stents (DESs) from January to December of 2009 at nine university hospitals were enrolled in this study. Mid-term angiographic and 12-month cumulative clinical outcomes of the TRI group (n = 220, 31.9%) were compared to those of the TFI group (n = 469, 28.1%).ResultsAfter propensity score matching, in-hospital complications and the 12-month major clinical outcomes during follow-up in the two groups were similar to each other. However, the incidence rates of repeat revascularization (6.4% vs. 0.5%, p = 0.003), target vessel revascularization (6.4% vs. 0.5%, p = 0.003), and major adverse cardiac events (MACE; 11.6% vs. 4.6%, p = 0.018) in the TFI group were higher than those in the TRI group during the 12-month of follow-up.ConclusionsIn our study, TRI in STEMI patients undergoing primary PCI with DESs was associated with lower incidence of access site hematoma, 12-month repeat revascularization, and MACE compared to TFI. Therefore, TRI might play an important role in reducing bleeding complications while improving major clinical outcomes in STEMI patients undergoing primary PCI with DESs.