High Risk Of Bleeding Complications Research Articles

Safety and efficacy of rivaroxaban compared with warfarin in patients undergoing peripheral arterial procedures

ObjectiveRivaroxaban is a United States Food and Drug Administration-approved oral anticoagulant for venous thromboembolic disease; however, there is no information regarding the safety and its efficacy to support its use in patients after open or endovascular arterial interventions. We report the safety and efficacy of rivaroxaban vs warfarin in patients undergoing peripheral arterial interventions. MethodsThis single-institution retrospective study analyzed all sequential patients from December 2012 to August 2014 (21 months) who were prescribed rivaroxaban or warfarin after a peripheral arterial procedure. Our study population was then compared using American College of Chest Physicians guidelines with patients then stratified as low, medium, or high risk for bleeding complications. Statistical analyses were performed using the Student t-test and χ2 test to compare demographics, readmissions because of bleeding, and the need for secondary interventions. Logistic regression models were used for analysis of variables associated with bleeding complications and secondary interventions. The Fisher exact test was used for power analysis. ResultsThere were 44 patients in the rivaroxaban group and 50 patients in the warfarin group. Differences between demographics and risk factors for bleeding between groups or reintervention rate were not statistically significant (P = .297). However, subgroup evaluation of the safety profile suggests that patients who were aged ≤65 years and on warfarin had an overall higher incidence of major bleeding (P = .020). Patients who were aged >65 years, undergoing open operation, had a significant risk for reintervention (P = .047) when they received rivaroxaban. ConclusionsReal-world experience using rivaroxaban and warfarin in patients after peripheral arterial procedures suggests a comparable safety and efficacy profile. Subgroup analysis of those requiring an open operation demonstrated a decreased bleeding risk when rivaroxaban was used (in those aged <65 years) but an increased risk for secondary interventions. Further studies with a larger cohort are required to validate our results.

Prevalence of Bleeding Complications Following Ultrasound-Guided Botulinum Toxin Injections in Patients on Anticoagulation or Antiplatelet Therapy

BackgroundPatients receiving anticoagulation or antiplatelet therapy may be at higher risk for bleeding complications following intramuscular chemodenervation injections. Musculoskeletal ultrasound may be able to reduce the risk of bleeding complications by providing real-time visualization of vascular structures and postinjection monitoring. Limited data exist addressing the risk of bleeding complications following ultrasound-guided botulinum neurotoxin intramuscular chemodenervation procedures in the setting of anticoagulation or antiplatelet therapy. ObjectiveTo provide initial outcome data regarding bleeding complications in patients on anticoagulation or antiplatelet therapy who have received ultrasound-guided botulinum neurotoxin intramuscular chemodenervation procedures. DesignRetrospective, medical record review. SettingAcademic institution outpatient spasticity clinic. ParticipantsTotal of 328 ultrasound-guided intramuscular botulinum toxin injections performed in 15 patients (mean age 53.8 years) with the predominant indication for chemodenervation being spastic paresis secondary to stroke. MethodsThe medical records of all patients undergoing ultrasound-guided intramuscular chemodenervation procedures performed between July 1, 2011, and October 16, 2015, were reviewed for demographic information, details regarding anticoagulation therapy, procedure specifics, and postinjection bleeding complications. All patients had a postinjection ultrasound to screen for hematoma. Main Outcome MeasuresPrevalence of clinically significant bleeding complications and of sonographically documented subclinical bleeding complications following ultrasound-guided chemodenervation procedures in patients on anticoagulation or antiplatelet therapy. ResultsOf 328 procedures, only 2 subclinical hematomas were detected, resulting in a bleeding complication rate of 0.61% in this patient population. The target muscles in these cases were tibialis posterior and pronator teres, and both cases were in patients on anticoagulation therapy (as opposed to antiplatelet therapy). ConclusionsThe risk of clinically significant bleeding complication appears to be very small following ultrasound-guided intramuscular chemodenervation procedures in the setting of systemic anticoagulation or antiplatelet therapy. Level of EvidenceIV

Venous thromboembolism — recommendations on the prevention, diagnostic approach and management. The 2017 Polish Consensus Statement

The 2017 Polish Consensus Statement (PCS 2017) includes updated recommendations on the prevention, diagnostic approach, and management of venous thromboembolism (VTE). For VTE without cancer, the authors of PCS 2017 recommend apixaban, edoxaban, rivaroxaban, and dabigatran over vitamin K antagonists (VKA) as long-term anticoagulant therapy. For VTE with cancer, the authors of PCS 2017 recommend low molecular weight heparins (LMWH) over VKA, apixaban, edoxaban, rivaroxaban and dabigatran. For extended secondary prevention of deep venous thrombosis (DVT), PCS 2017 recommends apixaban, edoxaban, rivaroxaban, dabigatran, VKA, and sulodexide. For extended secondary prevention of pulmonary embolism (PE), PCS 2017 recommends apixaban, edoxaban, rivaroxaban, dabigatran and VKA. For extended secondary prevention in patients with idiopathic DVT and a high risk of bleeding complications, the authors of PCS 2017 recommend NOT to stop anticoagulation and use sulodexide. For extended secondary prevention in patients with idiopathic PE and a high risk of bleeding, the authors of PCS 2017 recommend NOT to stop anticoagulation and suggest treatment with apixaban, edoxaban, rivaroxaban, and dabigatran in reduced doses adjusted to the risk of bleeding. For VTE treated with anticoagulants, PCS 2017 recommends against insertion of a vena cava filter. For patients with DVT, PCS 2017 suggests USING compression stockings routinely to prevent postthrombotic syndrome. For subsegmental PE without proximal DVT, PCS 2017 suggests clinical surveillance over anticoagulation with a low risk of recurrent VTE, and anticoagulation over clinical surveillance with a high risk of recurrent VTE. The 2017 Polish Consensus Statement suggests thrombolytic therapy for PE with hypotension, and systemic therapy over catheter-directed thrombolysis. For recurrent VTE on a non-LMWH anticoagulant, PCS 2017 suggests LMWH, and for recurrent DVT and/or PE on LMWH, PCS 2017 suggests increasing the dose of LMWH.

Pipeline flow diversion of ruptured blister aneurysms of the supraclinoid carotid artery using a single-device strategy.

OBJECTIVE Ruptured blister aneurysms remain challenging lesions for treatment due to their broad, shallow anatomy and thin, fragile wall. Historical challenges with both open microsurgical approaches and intrasaccular endovascular approaches have led to increased use of flow diversion for management of these aneurysms. However, the optimum paradigm, including timing of treatment, use of dual antiplatelet therapy, and number of flow-diverter devices to use remains unknown. The authors describe their experience with ruptured blister aneurysms treated with flow diversion at their institution, and discuss rates of rebleeding and number of devices used. METHODS All patients presenting with subarachnoid hemorrhage from a ruptured blister aneurysm and treated with Pipeline flow diversion were identified. Patient demographic data, clinical status and course, need for external ventricular drain (EVD), timing of treatment, and angiographic details and follow-up were recorded. RESULTS There were 13 patients identified (11 women and 2 men), and 4 had multiple aneurysms. Two aneurysms were treated on initial angiography, with average time to treatment of 3.1 days for the remainder, after discussion with the family and institution of dual antiplatelet therapy. Device placement was technically successful in all patients, with 2 patients receiving 2 devices and the remainder receiving 1 device. There was 1 intraoperative complication, of a wire perforation causing intracerebral hemorrhage requiring decompressive craniectomy. Three patients had required EVD placement for management of hydrocephalus. There was no rebleeding from the target lesion; however, one patient had worsening intraventricular hemorrhage and another had rupture of an unrecognized additional aneurysm, and both died. Of the other 11 patients, 10 made a good recovery, with 1 remaining in a vegetative state. Nine underwent follow-up angiography, with 5 achieving complete occlusion, 2 with reduced aneurysm size, and 2 requiring retreatment for aneurysm persistence or enlargement. There were no episodes of delayed rupture. CONCLUSIONS Pipeline flow diversion is a technically feasible and effective treatment for ruptured blister aneurysms, particularly in good-grade patients without hydrocephalus. Patients with a worse grade on presentation and requiring EVDs may have higher risk for bleeding complications and poor outcome. There was no rebleeding from the target lesion with use of a single device in this series.

Abstract 232: Minimizing Bleeding Complications in the Cardiac Catheterization Lab

Background: Bleeding complications related to invasive procedures significantly increase costs, length of stay, morbidity and mortality risk. The cardiac catheterization lab [CCL] is a high risk, high volume center requiring continuous monitoring to minimize the incidence of vascular injury, hematomas/ hemorrhage, blood transfusions. Oversight extends beyond the CCL to concerns regarding post procedure access management, appropriate medication administration, ambulation, threshold for transfusion, vascular diagnostics/consultation. Based on best practices a multidisciplinary team has developed and implemented a risk stratification tool, encourages best practices, and continues to collect data to provide feedback and process improvement. Methods: The Stony Brook U Hospital CCL serves a Suffolk Co population of &gt;1.5 million and provides 7x24 coverage for STEMI interventions over 912 square miles. Data post implementation of a bleeding risk stratification and optimal practices tool was collected from September of 2014 through September of 2015 to assess bleeding complication incidence [NCDR criteria], associations, and implementation of suggested practice improvements [radial access, bivalirudin, vascular closure). Results: A total of 1770 angioplasty procedures were performed during the monitored period [485 radial (27%), 1285 femoral (73%) approach]. In the femoral access group a total of 485 vascular closure devices (38%) were deployed. Bivalirudin [Angiomax] was used in 1,304 cases (74%); UFH was used in 466 cases (26%). Bleeding complications were identified in 69 patients during the monitored period [3.9% incidence]. Preprocedure risk screening identified 50 [72%] patients with bleeding complications as high risk and 19 [28%] patients as intermediate risk. In the patients with bleeding complications: Radial artery access was used in 16 (23%), bivalirudin in 63 (91%), vascular closure devices in 19 of appropriate femoral candidates (48%) with 12 femoral access patients (23%) receiving an Impella or IABP. Monthly case review has identified additional opportunities for improvement including: preprocedure optimization where possible, establishing transfusion thresholds, post procedure large sheathe/device management, and antithrombotic/antiplatelet medication administration. Conclusions: A bleeding complication task force developed a PCI bleeding risk assessment tool to identify patients at high risk of bleeding complications by NCDR criteria. Routine implementation accurately identifies high risk patients and encourages the use of best practices designed to reduce complications. Continued feedback, education and encouragement of practitioners and support staff in implementing best practices continues to improve implementation. Focused case review has provided additional opportunities for continued quality improvement.

APIXABAN IN THE TREATMENT OF ATRIAL FIBRILLATION: RANDOMIZED TRIALS AND EVERYDAY CLINICAL PRACTICE

Apixaban is the only NOA the administration of which is associated with a reduction in the incidence of both stroke and major bleeding. Therefore, apixaban is the drug of choice in patients with non-valvular AF, including elderly patients, patients with a high risk of bleeding complications, as well as in patients with impaired renal function. In clinical practice, the efficacy and safety of apixaban are not inferior to those obtained in the ARISTOTLE trial. Apixaban is safe when used during cardioversion and catheter ablation. The results of pre-clinical studies provide implications for further investigation into the possibility of administration of apixaban in patients with «valvular» AF.

Effect of the AN69ST membrane versus citrate-enriched dialysate on clotting events in hemodialysis without systemic anticoagulation

Introduction Anticoagulation minimizes clotting in the extracorporeal circuit during hemodialysis but becomes a problem in patients with a high risk of bleeding complications. Different methods can prevent coagulation of dialysis circuits. In this study, we compare the effects of the AN69ST membrane and citrate-enriched dialysate on clotting events during dialysis in patients with a high risk of bleeding. Patients and methods This retrospective study included 259 adults undergoing chronic hemodialysis and with a contraindication for using systemic heparinization: they had undergone renal transplantation or had a transplantectomy. They were hemodialyzed with AN69ST and acetate dialysate or with citrate-enriched dialysate and a polysulfone membrane. The primary outcome was defined as the need to interrupt a dialysis session because of clotting events. The secondary outcomes were the number of session with an increase of venous pressure and the variation of urea-reduction ratio. Results A total of 144 patients were included in the AN69ST group and 115 patients in the citrate group. No significant difference was noted between the groups regarding premature termination of a dialysis session. No bleeding was noted. Urea-reduction ratio and variation in venous pressure during the session were significantly better in citrate-enriched dialysate group (P Discussion An AN69ST membrane with acetate dialysate was as effective as citrate-enriched dialysate with a polysulfone high-flux membrane with regards to premature termination of a dialysis session. However, urea-reduction ratio was significantly better and there were fewer cases of increased venous pressure in the citrate group (P Conclusion An AN69ST membrane with acetate dialysate was as effective as citrate-enriched dialysate with a polysulfone high-flux membrane with regards to premature termination of a dialysis session. However, urea-reduction ratio was significantly better and there were fewer cases of increased venous pressure in the citrate group (P

Preclinical evaluation of a novel polyphosphazene surface modified stent

BackgroundTreatment options for patients with coronary artery disease at high risk for bleeding complications are limited. The aim of the current preclinical study was to evaluate neointimal coverage, endothelial recovery, inflammation and thrombogenicity in a novel thin-strut (71μm thickness) Cobalt Chromium (CoCr) stent modified with a nano-thin Polyzene®-F (PzF) surface coating. Methods and resultsTwenty-eight single PzF nano-coated stents and 20 bare metal control stents (BMS) were implanted in the coronary arteries of 24 pigs, with scheduled 5- (n=5), 28- (n=13), and 90-day (n=6) follow-up in addition to overlapping configuration (n=6 each), examined at 28-days. Histomorphometric analysis showed significantly lower neointimal thickness in PzF nano-coated stents than BMS controls at both 28- and 90-days (p=0.023 and 0.005) and reduced inflammation (p=0.06 and 0.13). Endothelial coverage over luminal surfaces at all time points was similar between nano-coated stents and BMS controls. We conducted supplementary in-vitro experiments using human monocytes and an ex-vivo swine carotid-jugular arterio-venous shunt model to better understand the healing properties afforded by the PzF nano-coating. Overall, the PzF-nano-coating showed reduced monocyte adhesion and thrombus formation compared to the un-coated controls. ConclusionsStents modified with a nano-thin PzF-coating implanted in healthy swine indicate favorable vascular healing properties shown by reduced neointimal hyperplasia and inflammation, along with resistance to thrombus formation in an ex-vivo shunt model over unmodified stents.

Atrial fibrillation and chronic kidney disease requiring hemodialysis — Does warfarin therapy improve the risks of this lethal combination?

IntroductionWarfarin therapy for stroke prevention is recommended for patients with AF, but its value in patients with chronic kidney disease on HD is unknown. MethodsThe anticoagulation regimens of patients with a prior history of AF hospitalized for initiation of chronic HD, and of patients receiving chronic HD who had a new diagnosis of AF between 2009 and 2012 were reviewed. Exclusions were renal transplant, peritoneal dialysis, rheumatic valve disease, prosthetic heart valve, GI bleeding, malignancy with chemotherapy in last 6months or still undergoing treatment, a history of AF ablation, a history of ICD implantation, or those receiving warfarin for non-AF indications. ResultsAmong 302 patients included in the study, 119 (39%) were prescribed warfarin and 183 (61%) were not. The two groups were similar regarding demographics, and prevalence of comorbidities including diabetes, heart failure, coronary artery disease, hypertension, use of antiplatelet agents and prior stroke. Warfarin use did not lower risk for ischemic stroke (HR 0.93; 95% CI 0.49–1.82, P=0.88) or improve overall survival (HR 1.02; 95% CI 0.91–1.15, P=0.62), but trended toward higher risk of bleeding complications (HR 1.53; 95% CI 0.94–2.51, P=0.086) after adjusting for potential confounders. ConclusionWarfarin use was not associated with reduction in stroke risk or mortality in patients with AF on chronic HD, but trended toward greater bleeding risk. The benefit of warfarin therapy in these patients may be outweighed by its risks.

Implications of Frailty in Elderly Patients With Electrophysiological Conditions.

A growing number of complex older adults are referred for electrophysiological conditions and age alone is insufficient to guide management decisions such as implantable cardioverter-defibrillator (ICD) implantation or atrial fibrillation anticoagulation. The concept of frailty has emerged as a geriatric vital sign to gain insight into physiological reserve and prognostic risk beyond chronological age and comorbidities. To date, a number of published studies have evaluated frailty in patients with electrophysiological conditions. These studies collectively demonstrate that frail patients have an increased prevalence of atrial fibrillation, lower use of oral anticoagulation, higher risk of bleeding complications from oral anticoagulation, and higher risk of stroke and mortality. A paucity of studies have explored frailty in the setting of device implantation, with a signal suggesting that frail heart failure patients may have a lower likelihood of being considered for ICD and cardiac resynchronization therapy devices, and a higher risk of fatal and nonfatal events after ICDand cardiac resynchronization therapy implantation. Whether frailty modulates the risks and benefits of these devicesisacritical knowledge gap for which further study is clearly warranted.

BIVALIRUDIN FOR PERCUTANEOUS CORONARY INTERVENTIONS: REVIEW OF CURRENT GUIDELINES

Purpose. The purpose of this article was a review of contemporary international guidelines for the analysis of the evidence base for bivalirudin use as a medical support of percutaneous coronary intervention (PCI) in patients with different forms of coronary artery disease. Materials and methods. Based on a review of European and American guidelines for management and revascularization in patients with different forms of coronary artery disease of 2013, 2014 and 2015, the evidence base of bivalirudin use as a medical support for PCI in patients with different forms of coronary artery disease was analyzed. Results. The current evidence base for anticoagulant PCI support in patients with different forms of coronary artery disease means choosing safe and effective anticoagulant accordance to the profiles of ischemic and hemorrhagic risk. The direct thrombin inhibitor bivalirudin has a short half-life, predictable anticoagulant profile and has indications for use it in any form of coronary artery disease (Stable coronary artery disease, Non-STEMI and STEMI), based on a large number of randomized clinical trials. Conclusions . There is no doubt that bivalirudin for patients with stable coronary artery disease and heparin-induced thrombocytopenia and for a cohort of patients with a high risk of bleeding complications has benefits and efficacy. Bivalirudin as the anticoagulant support for PCI in non-STEMI patients has the highest class and level of evidence. Class and level of evidence for the use of bivalirudin as PCI support in STEMI patients in 2014 decreased to class IIa, level A however increased risk of acute stent thrombosis associated with the bivalirudin using in this group of patients does not lead to an increased risk of death compared with unfractionated heparin.

Circulation : Clinical Summaries

<i>Circulation</i> : Clinical Summaries

Abstract 205: Minimizing Post Procedural Bleeding Complications - A Quality Improvement Initiative

Objectives: The primary purpose of this study is to implement the National Cardiovascular Data Registry (NCDR) CathPCI bleeding risk score pre-procedurally, in order to identify the patients who are at high risk for bleeding complications and secondly, to examine accurate documentation to decrease hemorrhagic complications among adult patients undergoing percutaneous coronary intervention (PCI). Background: Bleeding is one of the most common complications of PCI. The NCDR CathPCI bleeding risk score can predict patient risk for bleeding complications pre-procedurally. This tool is recognized as an assessment tool that can modify bleeding risk among adult patients undergoing PCI. This validated, individualized bleeding risk score (BRS) is useful in clinical decision making to promote quality of care, patient safety, and patient satisfaction and PCI outcomes. Specific outcomes evaluated in this project include number of blood transfusion and length of stay (LOS). Currently, this BRS tool is under utilized in the clinical setting. Methods: A cross sectional study design was implemented for this quality improvement project in a major medical center in the Northeast. Retrospective clinical data review was conducted for adult patients who underwent PCI prior to initiation of the NCDR CathPCI assessment tool. A data collection form was implemented to obtain this retrospective data related to bleeding complications. The NCDR CathPCI bleeding score tool was then implemented for adult patients who underwent PCI. Prospective data collection after implementing NCDR cathPCI bleeding risk tool is in progress. Results: The preliminary findings of the retrospective data review prior to implementation of the NCDR CathPCI bleeding score suggests that, 34.4% of the patients who received blood transfusions had documented bleeding complications (hematoma 15.6% (10 of 64); retro-peritoneal bleeding 9.4% (6 of 64); gastrointestinal bleeding 9.4% (6 of 64). Only 14.1% (9 of 64) of these patients had a drop in hemoglobin of 3grams from the baseline prior to transfusion. There was also a lack of documentation of hematoma size. Chronically anemic patients who received blood transfusion without bleeding complications accounted for 65.6% (42 of 64) of the patients reviewed in the retrospective data review. Average LOS of patients who required blood transfusion was an average of 1.34 days when compared with patients who did not develop bleeding complications. Final results of the prospective data analysis post implementation of the NCDR CathPCI assessment tool are pending. Conclusion: Pending.

Statin Therapy and the Development of Cerebral Amyloid Angiopathy—A Rodent in Vivo Approach

Background: Cerebral amyloid angiopathy (CAA) is characterized by vascular deposition of amyloid β (Aβ) with a higher incidence of cerebral microbleeds (cMBs) and spontaneous hemorrhage. Since statins are known for their benefit in vascular disease we tested for the effect on CAA. Methods: APP23-transgenic mice received atorvastatin-supplemented food starting at the age of eight months (n = 13), 12 months (n = 7), and 16 months (n = 6), respectively. Controls (n = 16) received standard food only. At 24 months of age cMBs were determined with T2*-weighted 9.4T magnetic resonance imaging and graded by size. Results: Control mice displayed an average of 35 ± 18.5 cMBs (mean ± standard deviation), compared to 29.3 ± 9.8 in mice with eight months (p = 0.49), 24.9 ± 21.3 with 12 months (p = 0.26), and 27.8 ± 15.4 with 16 months of atorvastatin treatment (p = 0.27). In combined analysis treated mice showed lower absolute numbers (27.4 ± 15.6, p = 0.16) compared to controls and also after adjustment for cMB size (p = 0.13). Conclusion: Despite to a non-significant trend towards fewer cMBs our results failed to provide evidence for beneficial effects of long-term atorvastatin treatment in the APP23-transgenic mouse model of CAA. A higher risk for bleeding complications was not observed.

Venous thromboembolism in hematopoietic stem cell transplant recipients.

Venous thromboembolism (VTE) is an increasingly recognized problem in the post-hematopoietic stem cell transplantation (HSCT) setting, with a lack of high-quality evidence-based data to recommend best practices. Few patients with hematologic malignancies and even fewer post-HSCT patients were included in randomized trials of VTE prophylaxis and treatment. Prior VTE, GVHD, infections and indwelling venous catheters are risk factors for thrombosis. The increasing use of post-transplant maintenance therapy with lenalidomide in patients with multiple myeloma adds to this risk after autologous HSCT. These patients are also at high risk of bleeding complications because of prolonged thrombocytopenia and managing the competing risks of bleeding and thrombosis can be challenging. This review aims to provide a practical, clinician-focused approach to the prevention and treatment of VTE in the post-HSCT setting.

Reduced Transfusion During OLT by POC Coagulation Management and TEG Functional Fibrinogen: A Retrospective Observational Study.

Patients undergoing orthotopic liver transplantation are at high risk of bleeding complications. Several Authors have shown that thromboelastography (TEG)-based coagulation management and the administration of fibrinogen concentrate reduce the need for blood transfusion. We conducted a single-center, retrospective cohort observational study (Modena Polyclinic, Italy) on 386 consecutive patients undergoing liver transplantation. We assessed the impact on resource consumption and patient survival after the introduction of a new TEG-based transfusion algorithm, requiring also the introduction of the fibrinogen functional thromboelastography test and a maximum amplitude of functional fibrinogen thromboelastography transfusion cutoff (7 mm) to direct in administering fibrinogen (2012-2014, n = 118) compared with a purely TEG-based algorithm previously used (2005-2011, n = 268). After 2012, there was a significant decrease in the use of homologous blood (1502 ± 1376 vs 794 ± 717 mL, P < 0.001), fresh frozen plasma (537 ± 798 vs 98 ± 375 mL, P < 0.001), and platelets (158 ± 280 vs 75 ± 148 mL, P < 0.005), whereas the use of fibrinogen increased (0.1 ± 0.5 vs 1.4 ± 1.8 g, P < 0.001). There were no significant differences in 30-day and 6-month survival between the 2 groups. The implementation of a new coagulation management method featuring the addition of the fibrinogen functional thromboelastography test to the TEG test according to an algorithm which provides for the administration of fibrinogen has helped in reducing the need for transfusion in patients undergoing liver transplantation with no impact on their survival.

Coagulation indices in very preterm infants from cord blood and postnatal samples

Very premature infants are at high risk of bleeding complications; however, few data exist on ranges for standard coagulation tests. The primary objective of this study was to measure standard plasma coagulation tests and thrombin generation in very premature infants compared with term infants. The secondary objective was to evaluate whether an association existed between coagulation indices and intraventricular hemorrhage (IVH). Cord and peripheral blood of neonates < 30 weeks gestational age (GA) was drawn at birth, on days 1 and 3 and fortnightly until 30 weeks corrected gestational age. Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen and coagulation factor levels were measured and tissue factor-stimulated thrombin generation was characterized. Control plasma was obtained from cord blood of term neonates. One hundred and sixteen infants were recruited. Median (range) GA was 27.7 (23.7-29.9) weeks and mean (SD) birth weight was 1020 (255) g. Median (5th-95th percentile) day 1 PT, APTT and fibrinogen were 17.5 (12.7-26.6) s, 78.7 (48.7-134.3) s and 1.4 (0.72-3.8) g L(-1) , respectively. No difference in endogenous thrombin potential between preterm and term plasma was observed, where samples were available. Levels of coagulation factors II, VII, IX and X, protein C, protein S and antithrombin were reduced in preterm compared with term plasma. Day 1 APTT and PT were not associated with IVH. In the largest cross-sectional study to date of very preterm infants, typical ranges for standard coagulation tests were determined. Despite long clotting times, thrombin generation was observed to be similar in very preterm and term infants.

A systematic review on the role of bivalirudin in patients undergoing percutaneous coronary interventions: primus inter pares or a falling star?

Intracoronary thrombosis triggered by ruptured or eroded atherosclerotic plaques constitutes the predominant underlying cause of acute coronary syndromes (ACS). Thrombin is considered a central enzyme in hemostasis and thrombosis, and a well-established target for anticoagulant therapies. Bivalirudin was introduced in the clinical practice as a promising, reversible, direct thrombin inhibitor with a predictable anticoagulant effect. Initial randomized clinical trials demonstrated that bivalirudin compared with heparin on top of a glycoprotein IIb/IIIa inhibitor was associated with a significant reduction of major bleeding and favorable net clinical outcomes in patients undergoing percutaneous coronary interventions (PCI). The HORIZON-AMI trial even indicated mortality benefit in bivalirudin-treated patients. Thereby, the 2011 and 2012 European Society of Cardiology Guidelines on the management of non-ST-segment elevation ACS and ST-segment elevation myocardial infarction positioned bivalirudin as the anticoagulant of choice in the PCI setting. Further randomized studies, better reflecting routine clinical practice, revealed significantly increased rates of stent thrombosis and myocardial infarction in the bivalirudin arm. Additionally, these findings were corroborated in the subsequent meta-analyses. Speculations that excessive occurrence of stent thrombosis and myocardial infarction may be caused by too short duration of post PCI bivalirudin infusion did not find confirmation in the latest MATRIX trial. In this systematic review, we aim to assess the efficacy and safety of bivalirudin therapy in patients undergoing PCI and to formulate recommendations on the bivalirudin use for clinicians. In our opinion, the research evidence and pharmacoeconomic considerations strongly support the use of bivalirudin in PCI patients at high risk of bleeding complications, while in other situations old and inexpensive UFH or enoxaparin remain the first line antithrombotic drugs.

Perioperative Management of Antiplatelets and Anticoagulants Among Patients Undergoing Elective Transurethral Resection of the Prostate--A Single Institution Experience.

To evaluate current practice in the perioperative management of antiplatelets (AP) and anticoagulants (AC) among men undergoing elective transurethral resection of the prostate (TURP), as well as the associated perioperative bleeding and thromboembolic complications. Retrospective review of consecutive elective TURP patients in a single tertiary institution from January 2011 to December 2013 (n = 293). Data on the regular use of AP/AC and the perioperative management approach were collected from patients' electronic medical records. Bleeding and thromboembolic complications were assessed up to 30 days postoperative. Association between AP/AC use and perioperative complications was assessed using the Kruskall-Wallis test (continuous variables) and the Fisher exact test (categoric variables). There were 107/293 (37%) patients receiving long-term AP while there were 25/293 (9%) patients receiving long-term AC. A total of 72/107 (67%) patients ceased AP on an average of 7.6 days preoperatively, while 35/107 (33%) continued receiving AP. Patients with coronary stents (62%) and coronary bypass graft (67%) were significantly more likely to continued receiving AP (P < 0.001). AC was ceased in all patients preoperatively, with 16/25 (64%) receiving enoxaparin bridging. Overall, there were 31 (10%) incidents of bleeding complications and 5 (2%) thromboembolic events. AC users who had enoxaparin bridging had significantly higher risk of bleeding complications (44%), compared with non-AP/AC users (8%), AP users who ceased AP (4%), AP users who continued receiving AP (17%), and AC users who did not receive enoxaparin bridging (0%) (P < 0.001). AC users who received enoxaparin bridging also reported significantly higher thromboembolic complications (17%; P < 0.001) and prolonged hospital stay (mean 5.4 days) (P = 0.002), compared with other patients. Perioperative management of AP/AC should be based on the indications and the American College of Chest Physicians thromboembolic risk stratification. Regular AC users who had enoxaparin bridging are at increased risk of both perioperative bleeding and thromboembolic complications.

Recent Advances in Optimal Adjunctive Antithrombotic Therapy in STEMI Patients Undergoing Primary Angioplasty: An Overview.

There has been a considerable effort to improve adjunctive antithrombotic therapies to reperfusion strategies in the treatment of ST-segment elevation Myocardial Infarction (STEMI). Therefore, the aim of this article is to provide a critical and updated overview of recent advances on adjunctive antithrombotic therapies in patients undergoing primary angioplasty for STEMI. Due to very low costs, early Unfractionated Heparin (UFH) plus additional periprocedural administration should still be regarded as the gold standard in antithrombotic therapy, whereas subsequent subcutaneous administration of Low Molecular Weight Heparins (LMWHs) or fondaparinux should be considered, especially in patients at higher risk of thromboembolic complications. Periprocedural bivalirudin should be considered instead of a strategy of combined UFH and Glycoprotein (Gp) IIb/IIIa inhibitors, especially among patients at higher risk of bleeding complications. New oral ADP antagonists should be administrated as early as possible soon after diagnosis, whereas the use of clopidogrel should be limited to the cases when the new ADP antagonists are not available or contraindicated. However, rivaroxaban has obtained indication for Acute Coronary Syndromes (ACS), and therefore its combination with aspirin and clopidogrel will gain recognition especially among STSegment Elevation Myocardial Infarction (STEMI) patients. Future trials are needed to compare different possible strategies with oral antithrombotic therapies and in particular optimal duration, especially in the era of new DES that have been shown to reduce the risk of stent thrombosis. Early Gp IIb/IIIa inhibitor use may be considered as upstream therapy especially in high-risk patients, whereas the choice of periprocedural administration may be based on thrombus burden or in case of impaired haemodynamic conditions that may compromise oral drug absorption. Overall, a more aggressive antithrombotic approach should be considered within the first hours from symptom onset, when the considerable viability justifies aggressiveness. The use of radial approach and potential protamine administration should be considered in order to minimize the risk of bleeding complications. Due to the very low mortality currently achieved by primary angioplasty and stenting, a further reduction in short or mediumterm mortality would be not easy to demonstrate. Therefore, additional endpoints, such as infarct size and myocardial perfusion, may be considered in future randomized trials especially for the evaluation of new periprocedural antithrombotic therapies among patients undergoing mechanical revascularization for STEMI.