Prevent Bleeding Complications Research Articles

Role of coagulation profile in prevention of bleeding complications in primary total knee arthroplasty patients

Introduction: Incidence of deep vein thrombosis (DVT) (1.9%-3%) and pulmonary embolism (PE) (0.01%) post total knee arthroplasty (TKA) in Asian population is less compared to western population (85% and 1.5%-10% respectively). Hence, routine chemoprophylaxis following Western protocols is debatable in Asia. Wound complications like bleeding, hematoma, blisters, skin necrosis are high with low molecular weight heparin (LMWH) as compared with Aspirin. Aspirin is associated with low rate of DVT and PE (0.008% - 0.35%). The aim is to study the coagulation profile and adverse events like DVT, PE and wound complications in postoperative TKA patients on pharmacological DVT prophylaxis and watch for correlation between coagulation parameters and bleeding complications, and accordingly administer thromboprophylactic agents. Methods: Prospective observational study. 463 patients undergoing primary unilateral TKA were bifurcated into groups according to thromboprophylaxis given by two surgeons. 1. 271 patients received LMWH 2. 192 patients received Aspirin Patients were evaluated with coagulation profile preoperatively and postoperatively and observed for wound complications, DVT and PE. Results: The use of LMWH conferred a significantly higher incidence of wound soakage (p

Anticoagulation Control in Older Atrial Fibrillation Patients Receiving Vitamin K Antagonist Therapy for Stroke Prevention.

Introduction Efficacy and safety of vitamin K antagonists (VKAs) among atrial fibrillation (AF) patients are enhanced when the International Normalised Ratio (INR) is 2.0–3.0. Anticoagulation control among older patients is perceived to be lower and contributes to poorer initiation and uptake. Objective To examine the quality of INR control, adverse clinical outcomes, and factors associated with bleeding in older AF patients (≥80 years). Methods Anticoagulation control assessed by time in therapeutic range (TTR) (Rosendaal method) and percentage INRs in range (PINRR). Among the 205 patients aged ≥80 years, 58.5% were female, with mean (SD) CHA2DS2-VASc 4.4 (1.3) and HAS-BLED 1.8 (0.8) scores. Results Mean (SD) TTR and PINRR were similar for those aged ≥80 vs. <80 years (66.7 (13.8) vs. 66.7 (13.1)) despite significantly lower INR monitoring intensity (51.2 (22.7) vs. 60.7 (25.8)) and shorter follow-up (4.4 (2.6–6.2) vs. 5.7 years (3.3–7.1)) in those ≥80 years of age. Good anticoagulation control (TTR and PINRR ≥70%) of 44% was seen in both age groups. No significant differences in composite major adverse clinical events were evident for those aged ≥80 vs. <80 years (p = 0.55). Cox regression analysis confirmed that age ≥80 years was associated with higher risk of bleeding (HR 1.90 (1.01–3.56); p = 0.047). Conclusions Suboptimal (TTR and PINRR <70%) anticoagulation control was evident in all patients. Risk of bleeding increased, but there was no difference in thromboembolic events and all-cause mortality in those aged ≥80 years. Improving TTR to ≥70% and enhancing anticoagulation monitoring of VKA use remain a clinical priority to prevent bleeding complications, particularly among those aged 80 years and above.

Factors Associated with Nonachievement of Target Blood Pressure in Patients on Antithrombotic Therapy: A Real-World Study.

Introduction: The current guidelines for managing hypertension recommend strict blood pressure (BP) control to prevent bleeding complications in patients with hypertension on antithrombotic therapy. However, the target BP value of <130/80 mmHg is achieved in a small proportion of these patients. This study aimed to examine the factors associated with nonachievement of target BP value (≥130/80 mmHg) in patients on antithrombotic therapy. Methods: This retrospective study was conducted at an outpatient clinic in 2018. Clinical parameters were obtained from the center’s electronic medical database. Office BP was measured once in the sitting position. A target BP value of <130/80 mmHg was defined according to the Japanese Society of Hypertension Guidelines for the Management of Hypertension 2019. Results: Of the 26,803 outpatients who had scheduled visits during this time, 2,427 received antithrombotic therapy. Patients with chronic kidney disease stage 5 or on hemodialysis and those with missing data on body mass index were excluded from the study; eventually, 2,201 outpatients met the inclusion criteria. BP values of <140/90 mmHg were observed in 59.2% of these outpatients; however, only 30.6% displayed the target BP value of <130/80 mmHg. Univariate and multivariate logistic regression analyses indicated that male gender and obesity significantly correlated with nonachievement of the target BP (≥130/80 mmHg). However, heart failure and ischemic heart disease were negatively but significantly related to nonachievement of the target BP. Conclusions: The target BP value was achieved in only a small proportion of the patients treated with antithrombotic drugs. In patients on antithrombotic therapy, obesity appeared to be a modifiable risk factor, whereas cardiovascular comorbidities, such as heart failure, were negative factors contributing to nonachievement of the target BP.

Role of acquired von Willebrand syndrome in the development of bleeding complications in patients treated with Impella RP devices

Axial flow pumps are standard treatment in cases of cardiogenic shock and high-risk interventions in cardiology and cardiac surgery, although the optimal anticoagulation strategy remains unclear. We evaluated whether laboratory findings could predict bleeding complications and acquired von Willebrand syndrome (avWS) among patients who were treated using axial flow pumps. We retrospectively evaluated 60 consecutive patients who received Impella devices (Impella RP: n = 20, Impella CP/5.0: n = 40; Abiomed Inc., Danvers, USA) between January 2019 and December 2020. Thirty-two patients (53.3%) experienced major or fatal bleeding complications (Bleeding Academic Research Consortium score of > 3) despite intravenous heparin being used to maintain normal activated partial thromboplastin times (40–50 s). Extensive testing was performed for 28 patients with bleeding complications (87.5%). Relative to patients with left ventricular support, patients with right ventricular support were less likely to develop avWS (87.5% vs. 58.8%, p = 0.035). Bleeding was significantly associated with avWS (odds ratio [OR]: 20.8, 95% confidence interval [CI]: 3.3–128.5; p = 0.001) and treatment duration (OR: 1.3, 95% CI 1.09–1.55; p = 0.003). Patients with avWS had longer Impella treatment than patients without avWS (2 days [1–4.7 days] vs. 7.3 days [3.2–13.0 days]). Bleeding complications during Impella support were associated with avWS in our cohort, while aPTT monitoring was not sufficient to prevent bleeding complications. A more targeted anticoagulation monitoring might be needed for patients who receive Impella devices.

Abstract 12248: Dosing of Direct Oral Anticoagulants in Patients With Non-Valvular Atrial Fibrillation and Renal Dysfunction

Introduction: Reduced doses of direct oral anticoagulants (DOACs) are approved to prevent bleeding complications in specified populations of patients with non-valvular atrial fibrillation (NVAF). Little is known about the accuracy of DOAC dosing in patients with renal dysfunction. Hypothesis: We hypothesized that NVAF patients with renal dysfunction would be more likely to receive an inappropriate dose of a DOAC compared with patients with normal renal function. Methods: We examined all patients who had at least two claims for NVAF between 2015 and 2017 in the Symphony Health claims dataset. We defined under-dosing as patients treated with a reduced dose without meeting label specified criteria for dose reduction, and excess dosing as patients treated with a full dose despite meeting criteria for dose reduction. We performed a logistic regression model to measure the effect of CrCl on DOAC dosing. Results: Among 86,919 patients with NVAF and CHA 2 DS 2 -VASc &gt; 2, 12.3% were underdosed and 5.0% were excess dosed. Patients who received excess-dosed or under-dosed DOACs were older and more likely to have comorbidities such as heart failure or history of prior stroke (all p&lt;0.001), compared with patients who were appropriately dosed. Among patients with CrCl &gt; 60 ml/min, under-dosing occurred in 9% of patients, highest among patients treated with edoxaban (18%) and rivaroxaban (10.4%). Under-dosing rates were higher among patients with CrCl 30-59 ml/min, especially for apixaban and dabigatran ( Table) . Excess dosing occurred in approximately 1 in 5 patients with CrCl &lt;30 ml/min. For every 10 unit decrease in CrCl, the odds of the patient receiving an inappropriately dosed DOAC increased by 27%. Conclusions: Incorrect DOAC dosing was observed in a substantial number of patients with NVAF in this large national study. Dosing errors occurred more frequently in patients with lower renal function, suggesting the need for efforts to improve effective and safe dosing of DOACs.

Uterine Extra-Abdominal Exposure in the Management of Anterior Placenta Previa and Accreta to Proceed Hysterotomy

The rates of placenta praevia and accreta are rising, probably as a result of increasing rates of cesarean delivery, as well as maternal age and assisted reproductive technologyIn this paper, we present a case report of a pregnancy complicated by anterior placenta praevia and accreta, in which the uterine extra-abdominal exposure technique was used to proceed the hysterotomy in the uterine fundus in order to avoid excessive bleeding and also to better evaluate the lower segment and consequent hysterectomy requirement. The main objective of this procedure is to describe a surgical technique which should guide the hysterotomy, in a position far enough away from the placenta site (fundus or posterior), in order to prevent bleeding complications in placental accreta disorders.

59. The incidence of ischemic and hemorrhagic complications associated with ceasing vs maintaining anticoagulant and/or antiplatelet agents for spine pain interventions targeting the facet joint

<h3>BACKGROUND CONTEXT</h3> Facet joint interventions include medial branch blocks (MBB), radiofrequency ablation (RFA) and facet joint intra-articular injections (IA). Currently, American Society for Regional Anesthesia (ASRA) guidelines list these procedures as intermediate risk for the cervical and thoracic spine and low risk for lumbar spine. Accordingly, these guidelines recommend many anticoagulation (AC) medications and antiplatelet (AP) medications to be held or consideration made to hold for these procedures, presumably to mitigate the theoretical risk of a major bleeding complication. This is despite the fact there are few if any reports of serious bleeding complications that occur with these procedures, regardless of a patients AP or AC status. On the other hand, there is growing evidence suggests that the thrombotic complication risk of stopping these AC/AP medications for patients undergoing these facet joint interventions may exceed the hemorrhagic risk of maintaining them. <h3>PURPOSE</h3> The primary objective is to determine the risk of serious bleeding complications in patients undergoing facet targeted injections. The secondary objective is to determine if this is affected by the management of AC/AP medications. <h3>STUDY DESIGN/SETTING</h3> Retroscpective observational study. <h3>PATIENT SAMPLE</h3> A total of 6,598 facet joint interventions. <h3>OUTCOME MEASURES</h3> Bleeding or hemorrhagic complications within 90 days of intervention. <h3>METHODS</h3> A retrospective observational study was conducted in a private pain practice. Consecutive patients were identified between September 19, 2009 and June 16, 2017, and it was noted if they were taking AC/AP medications prior to a procedure and how these medications were managed. In patients on AC/AP medications, charts were thoroughly reviewed for thrombotic and/or hemorrhagic complications occurring within 90 days of the procedure. For all other patients not on AC/AP medications, only the rate of clinically significant hemorrhagic events were considered given there is no inherent risk of thrombosis related to facet targeted interventions. <h3>RESULTS</h3> A total of 6,598 facet joint interventions were identified. No clinically significant bleeding complications were noted noted. Of the patient sample, 581 interventions were performed on patients prescribed AC/AP medications, with only one patient was lost to follow up. In 126 of these cases, they were performed after patients ceased AC/AP medications, with no complications noted. AC/AP medications were continued in 455 cases, also with no bleeding complications noted. Interestingly, of the 581 cases three thrombotic complications were noted in the group that had maintained AC/AP medications. <h3>CONCLUSIONS</h3> In this large cohort of 6,598 cervical, thoracic, and lumbar facet targeted interventions, no cases of clinically significant bleeding complications were noted. This include no cases of clinically significant bleeding in the 581 cases in which patients were on AC/AP medications, of which 455 were continued on such medications. This suggests the overall risk of significant bleeding complications with these procedures is exceedingly low. This must be considered when managing patients on AC/AP medications, as while preventing bleeding complications is important, the risk of thrombotic complications in this patient populations may be higher. This data builds upon previous research and supports individualized perioperative risk assessment when making the decision to stop or continue AC/AP medications. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

Schwannoma in Hemophilic Patient: Surgical Considerations

Introduction: Schwannoma is a benign, encapsulated, tumor that arises from Schwann cells of myelinated nerves. In this report, we present a case of schwannoma in a hemophilic patient and its surgical considerations related to bleeding complications. Case Presentation: We present a case of a 27-year-old male coming to our center with a chief complaint of a painless, non-progressive growing mass on the back of his head since a year prior to admission. Physical examination showed that the mass was mobile, firm, and had a welldefined margin beneath the scalp. His radiograph showed a soft tissue mass beneath the scalp. MRI demonstrated a dense-multilobulated mass without intracranial infiltration. The patient had hemophilia A from the age of 5. We performed marginal excision of the mass with regiments of factor VIII (FVIII) concentrates preoperatively, intraoperatively, and postoperatively. Pathology was consistent with schwannoma.Conclusions: Schwannoma management in hemophilic patients needs several considerations. Perioperative planning plays a major part in the management of patients with tumors and hemophilia to prevent bleeding complications.

Incidence and Dosimetric Predictors of Radiation-Induced Gastric Bleeding After Chemoradiation for Esophageal and Gastroesophageal Junction Cancer

PurposeTo determine the incidence and predictors of gastric bleeding after chemoradiation for esophageal or gastroesophageal junction cancer. Methods and MaterialsWe reviewed patients receiving chemoradiation to at least 41.4 Gy for localized esophageal cancer whose fields included the stomach and who did not undergo surgical resection. The primary endpoint was grade ≥3 gastric hemorrhage (GB3+). Comprehensive stomach dose-volume parameters were collected, and stomach dose-volume histograms were generated for analysis. ResultsA total of 145 patients met our inclusion criteria. Median prescribed dose was 50.4 Gy (range, 41.4-56 Gy). Median stomach Dmax was 53.0 Gy (1.0-62.7 Gy), and median stomach V40, V45, and V50 Gy were 112 cm3 (0-667 cm3), 84 cm3 (0-632 cm3), and 50 cm3 (0-565 cm3), respectively. Two patients (1.4%) developed radiation-induced GB3+. The only dosimetric factor that was significantly different for these patients was a higher stomach Dmax (58.1 and 58.3 Gy) than the cohort median (53 Gy). One of these patients also had cirrhosis, and the other had a history of nonsteroidal anti-inflammatory drug use. Five other patients had GB3+ events associated with documented tumor progression. A Cox proportional hazards model based on stomach Dmax with respect to the development of GB3+ was found to be statistically significant. Time-to-event curves and dose-volume atlases were generated, demonstrating an increased risk of GB3+ only when stomach Dmax was >58 Gy (P < .05). ConclusionsWe observed a low rate of GB3+ events in patients who received chemoradiation to a median dose of 50.4 Gy to volumes that included a significant portion of the stomach. These results suggest that when prescribing 50.4 Gy for esophageal cancer, there is no need to minimize the irradiated gastric volume or dose for the sake of preventing bleeding complications. Limiting stomach maximum doses to <58 Gy may also avoid bleeding, and particular caution should be taken in patients with other risk factors for bleeding, such as cirrhosis.

Reducing antithrombotic-related bleeding risk in urgent and emergency cardiac surgery.

This review focuses on the role of CytoSorb® (CytoSorbents Corporation, Monmouth Junction, New Jersey, USA), a technology for purifying extracorporeal blood. The technology is designed for several indications to prevent bleeding complications during on-pump cardiac surgery, including removal of the antiplatelet agent, ticagrelor, and the oral anticoagulant, rivaroxaban, from the blood. Recent clinical studies are briefly reviewed.

Successful management of a severe factor X deficiency patient with amyloidosis undergoing renal biopsy

Introduction: Systemic amyloidosis is a disease with a high risk of bleeding. The mechanism of bleeding is complex and involves multiple factors including amyloid-relating coagulopathy, platelet dysfunction and abnormal structural changes of arterioles. Among these, acquired coagulation factor X deficiency is the most common coagulopathy. Fatal bleeding may be associated with severe factor X deficiency particularly in the perioperative setting following invasive procedures. For the diagnosis of systemic amyloidosis, an invasive tissue biopsy is indispensable, and this procedure also requires close monitoring to prevent bleeding complications associated with factor X deficiency. Patient concerns: A 38-year-old Chinese man who developed nephrotic syndrome with both obviously prolonged prothrombin and activated partial thromboplastin time was admitted for further investigation. He also complained mild gingival hamorrhage intermittently for nearly 1 year. Diagnosis: The patient was diagnosed with a severe deficiency of coagulation factor X with factor X levels at 12.9%. The serum free lambda light chain was slightly elevated. A diagnosis of systemic amyloidosis was suspected. But no myocardial hypertrophy was observed. There was neither hepatomegaly nor splenomegaly. No signs of amyloidosis and plasma cells abnormality were found by routine analysis of bone marrow and abdominal fat pad biopsy samples. Interventions: After administration of low-dose prothrombin complex concentrates which lead rise to 27.4% in factor X level, the patient underwent kidney biopsy successfully without the occurrence of major bleeding and thrombotic events. The final pathological diagnosis was renal lambda light chain amyloidosis. Outcomes: No gross hemoturia, perirenal hematoma, and a thrombotic event occurred during his hospital stay after the kidney biopsy. For further management, the patient has been advised for autologous stem cell transplantation. Conclusion: This case report presents a rare occurrence of severe factor X deficiency in a patient diagnosed with amyloidosis. Overall coagulation state assessment before invasive procedure is helpful for bleeding-risk stratification and hemostatic-dose formulation. Proper dosage of prothrombin complex concentrates can be safe and effective in preventing factor X-related bleeding complications.

Abstract 13722: There Will be Blood: A Cautionary Tale of Triple Therapy

A 54-year-old man with coronary artery disease, chronic kidney disease, atrial flutter, and chronic right internal carotid artery (ICA) occlusion was transferred to our institution for management of cardiogenic shock following an anterior ST-elevation myocardial infarction status post percutaneous coronary intervention of the left main coronary artery (LMCA). He was placed on short-term triple antithrombotic therapy. On the day before discharge, he acutely developed left sided neurological deficits and hypotension. Exam was concerning for a right hemispheric stroke. Labs revealed a creatinine of 2.8 mg/dL, INR of 3.7, and a hemoglobin of 6.6 g/dL (previously 10 g/dL). Prior to sending the patient for brain imaging, we performed a bedside echocardiogram to further evaluate his hypotension. This revealed a large pericardial effusion with tamponade physiology. We suspected hemorrhagic cardiac tamponade secondary to triple antithrombotic therapy. His hypotension initially responded to intravenous fluids and packed red blood cells, resulting in an improved neurologic exam and supporting our hypothesis that his deficits represented right cerebral hemispheric hypoperfusion in the setting of a known right ICA occlusion and tamponade. Pericardiocentesis was initially deferred, as the risk of bleeding appeared prohibitive without reversal of apixaban and his coagulopathy, and these measures would subject the patient to a significant risk of thrombosis (e.g. LMCA stent thrombosis). Unfortunately, the patient developed progressive shock. After careful informed consent, we proceeded with high-risk pericardiocentesis involving pre-procedural reversal of apixaban with andexanet alfa and successful evacuation of 300 ml of hemorrhagic fluid. The pericardial pressure improved from 24 mmHg to 4 mmHg with complete resolution of the patient’s shock and neurological deficits. Our case demonstrates the risks associated with triple antithrombotic therapy as well as the nuanced clinical decision-making and risk-benefit assessment required when considering the use of anticoagulant reversal agents to prevent bleeding complications in the context of recent ischemic events and the need for urgent invasive procedures.

Oxidative Stress and Preeclampsia-Associated Prothrombotic State.

Preeclampsia (PE) is a common obstetric disease characterized by hypertension, proteinuria, and multi-system dysfunction. It endangers both maternal and fetal health. Although hemostasis is critical for preventing bleeding complications during pregnancy, delivery, and post-partum, PE patients often develop a severe prothrombotic state, potentially resulting in life-threatening thrombosis and thromboembolism. The cause of this thrombotic complication is multi-factorial, involving endothelial cells, platelets, adhesive ligands, coagulation, and fibrinolysis. Increasing evidence has shown that hemostatic cells and factors undergo oxidative modifications during the systemic inflammation found in PE patients. However, it is largely unknown how these oxidative modifications of hemostasis contribute to development of the PE-associated prothrombotic state. This knowledge gap has significantly hindered the development of predictive markers, preventive measures, and therapeutic agents to protect women during pregnancy. Here we summarize reports in the literature regarding the effects of oxidative stress and antioxidants on systemic hemostasis, with emphasis on the condition of PE.

A Pilot Study to Evaluate the Feasibility of Anti-Fibrinolytic Agents in Reducing Hemorrhagic Complications in Pediatric Patients with Thrombocytopenia

Background: The risk of bleeding remains high in thrombocytopenic pediatric hematology-oncology patients despite the use of prophylactic platelet transfusions. In one study, WHO grade 2 or higher bleeding occurred in &amp;gt;80% of pediatric subjects receiving hematopoietic stem cell transplantation or chemotherapy despite a platelet transfusion threshold of 10,000/µl. The risk of bleeding is not decreased with higher transfusion thresholds or increased platelet doses. Bleeding episodes are associated with increased mortality rates, greater utilization of resources and increased transfusion requirements. We examined the use of anti-fibrinolytic agents in decreasing bleeding events and platelet transfusions. Methods: We conducted a randomized double-blinded Phase 2 trial of tranexamic acid versus placebo in inpatient pediatric patients undergoing chemotherapy or HSCT expected to have prolonged thrombocytopenia. All patients admitted to the Oncology or HSCT services were screened for eligibility. Patients consenting for enrollment received either tranexamic acid 10m/kg/dose or normal saline every 8 hours while the platelet count as &amp;lt;30,000/ul until discharge or spontaneous platelet recovery (maximum 30 days). We conducted daily hemostatic assessments using the WHO bleeding scale and monitored adverse events and platelet transfusion requirements. Follow-up assessments took place at 7 and 30 days following completion of study medication. Primary aims were to assess safety and feasibility of tranexamic acid in children with hypoproliferative thrombocytopenia. Results: We screened 697 admissions over 11 months, 31 patients were eligible for enrollment. Enrollment was suspended in March 2020 for COVID reasons though screening continued through July 2020. An additional 10 eligible patients were identified in this period. The most common reasons for ineligibility included recent asparaginase administration, predicted inpatient stay &amp;lt;5 days and age ≤ 2 or ≥ 18 years. Eleven patients enrolled and completed all study procedures. There were no missed doses of medication, 88.4% of doses were administered within one hour of prescribed time. Patients remained on study for a mean of 11.1 days. Five patients each met criteria for spontaneous platelet count recovery or discharge, 1 patient received the study medication for 30 days. Bleeding (all grades) occurred on 29.5% of days. Grade 2 or higher bleeding occurred on 4.9% of days and was experienced by 27.3% of patients. The most common sites of bleeding were oral/nasal and cutaneous. Subjects received a median of 2 platelet transfusions per patient. There were no thromboembolic events or serious adverse events. Conclusion: Tranexamic acid is well tolerated can be safely administered to pediatric oncology patients as an adjunct to therapy. We are planning a multi-center randomized controlled trial to assess the efficacy of tranexamic acid in reducing bleeding complications in this population. Disclosures Triulzi: Fresenius Kabi: Consultancy; Cerus Corp: Research Funding. OffLabel Disclosure: Tranexamic Acid - This medication is being studied as an adjuvant to therapy to prevent bleeding complications and reduce platelet transfusions in pediatric patients with hypoproliferative thrombocytopenia.

(S029) Managing therapeutic anticoagulation in bariatric surgery patients.

Patients that undergo bariatric surgery are at risk of bleeding. Some obesity-related comorbidities including venous thromboembolism and heart disease can often require therapeutic anticoagulation. Previous small institutional studies have demonstrated that bariatric surgery can be performed in this patient population. This study attempts to identify best practices in stopping and restarting therapeutic anticoagulation in patients undergoing bariatric surgery. A retrospective analysis was completed of our institution's database using anticoagulant medications to identify patients on therapeutic anticoagulation. Patients not on therapeutic anticoagulation were excluded, as well as patients that were started on therapeutic anticoagulation only in the post-operative period or those whose anticoagulation was stopped and not restarted. Indications for anticoagulation were recorded, as well as patient demographics and comorbid conditions. The patient chart was examined for when anticoagulation was stopped before surgery, when it was restarted after surgery, and whether or not the patient was therapeutically bridged. Baseline and post-operative hemoglobin values were recorded, as well as bleeding events, transfusions, reoperation, length of stay, and readmissions. Binary variables were compared across groups using Chi-square and Fisher's exact tests, and continuous variables were analyzed using T test. There were 2933 bariatric operations performed between January 1, 2012 and August 31, 2019. Of these patients, 64 were on therapeutic anticoagulation before and after the operation for one or more indications, including history of VTE (39), atrial fibrillation (27), clotting disorder (6), ventricular assist device (5), previous PCI (4), or mechanical valve (2). There were 4 (6.2%) patients that experienced bleeding events. All four patients were on Coumadin pre-operatively. Three patients experienced extraluminal bleeding, and one patient had intraluminal bleeding, and all events occurred within 72h of the operation. All four patients had their anticoagulation restarted prior to the bleeding event becoming evident, with anticoagulation in these patients restarted an average of 1.25days after surgery. There were no conditions that predisposed a patient to bleeding. There was no significant difference in amount of time anticoagulation was stopped before surgery in bleeding versus non-bleeding patients, and there appeared to be no increased risk of bleeding in patients that were on therapeutic bridging therapy. There were no thrombotic complications from the interruption in anticoagulation therapy. Bariatric surgery can be safely performed in patients on therapeutic anticoagulation, though this population is at greater risk for bleeding complications in the perioperative period. Meticulous hemostasis in the operating room is the most important aspect of preventing bleeding complications.

Haemostatic efficacy of single-dose factor administration in neonates with severe haemophilia undergoing circumcision.

Perioperative management of children with haemophilia undergoing surgery is a complex and understudied topic. Circumcision is the most common procedure performed in the neonatal period, and guidelines to prevent bleeding complications from circumcision are lacking. Treatment protocols vary widely, and many centres treat patients with factor products for up to two weeks after circumcision. There is an unmet need for studies evaluating optimal factor replacement therapy around the time of circumcision in neonates with severe haemophilia. To determine the efficacy of a single dose of factor replacement before circumcision to prevent bleeding complications in neonates with severe haemophilia. We conducted a retrospective chart review of male infants born between January 2000 and June 2019. Male neonates with severe haemophilia diagnosed at the Iowa Hemophilia and Thrombosis Center (n=22) and healthy newborn controls who underwent circumcision at the University of Iowa Hospitals were included. Data were collected from the electronic medical record. Neonates with severe haemophilia were separated into two groups-those pretreated with one dose of factor replacement before circumcision and those without pretreatment. We observed that neonates with severe haemophilia pretreated with a single dose of factor VIII or factor IX replacement had significantly reduced bleeding complications, shorter hospital stay and required less therapeutic intervention compared with untreated patients. Importantly, pretreated patients had outcomes similar to healthy controls. Our results demonstrate that a single dose of factor replacement before circumcision is effective to prevent bleeding in neonates with severe haemophilia.

International normalized ratio (INR) values in patients receiving oral vitamin K antagonists and undergoing oral surgery: A clinical audit.

Dental extractions can be safely carried out on patients under vitamin K antagonists (VKAs) therapy, without stopping or changing the dosage, but the international normalized ratio (INR) needs to be monitored on the day of the intervention, showing adequate rates before proceeding. This study aims at evaluating INR values, measured before oral surgery procedures, to assess the rate of patients, under VKAs therapy, outside the therapeutic range. A clinical audit was carried out involving patients under VKAs, who needed minor oral surgery procedures, over a period of 18 months. The patient was instructed to not modify or suspend VKAs prior to the intervention. Before surgery, each patient fulfilled a questionnaire on dietary and oral hygiene habits, and a blood sample was collected for INR assessment (cut-off value for surgical procedure ≤3.5). One hundred twenty-two patients were enrolled: 69 (56.6%) had an INR value within the established therapeutic range, 53 (43.4%) were out of range. No intra- or postsurgical major bleeding was recorded. INR, measured on the same day of oral surgery, has the potential to prevent bleeding complications by the identification of those patients out of range, who may require adjusting the drug therapeutic dosage.

Targeting Biological Polyanions in Blood: Strategies toward the Design of Therapeutics.

In this Review, we highlight well-described and emerging polyanions, and the way these molecules can be targeted in the design of potential therapeutics (synthetic and biologics) with applications in thrombosis and hemostasis. It is important to strike a balance between bleeding and clotting. In thrombosis, unwanted blood clots are formed in the lumen of a blood vessel, obstructing the flow of blood through the circulatory system. Over many years of research, several polyanionic biopolymers that can either impede (anticoagulant) or promote (procoagulant) blood clotting have been identified. Mediators impeding blood clotting, including polyanionic polysaccharides such as heparins and heparin mimics, are widely used as antithrombotics, although they impart adverse complications such as bleeding. Emerging synthetic polycations and well-described cationic proteins that are specifically designed to neutralize the biological activity of heparins to prevent bleeding complications are discussed. On the other hand, there is growing evidence that several polyanions bear a procoagulant nature in blood; polyphosphate (polyP), neutrophil extracellular traps (NETs), extracellular RNA, and cell-free DNA are shown to promote blood clotting. Recent research highlights the use of polycations and enzymes that either inhibit or cleave these procoagulant polyanions and demonstrates the proof-of-concept design of new antithrombotics without bleeding side effects. Additional studies have shown that some of these procoagulant polyanions can be used as a hemostat to prevent bleeding in an emergency. There are significant opportunities for chemists in the design of new inhibitors and agents with improved selectivity toward these biological polyanions, furthering the development of novel therapeutics.

Direct oral anticoagulant plasma levels’ striking increase in severe COVID‐19 respiratory syndrome patients treated with antiviral agents: The Cremona experience

BackgroundAntiviral drugs are administered in patients with severe COVID‐19 respiratory syndrome, including those treated with direct oral anticoagulants (DOACs). Concomitant administration of antiviral agents has the potential to increase their plasma concentration. A series of patients managed in the Cremona Thrombosis Center were admitted at Cremona Hospital for SARS‐CoV‐2 and started antiviral drugs without stopping DOAC therapy. DOAC plasma levels were measured in hospital and results compared with those recorded before hospitalization. MethodsAll consecutive patients on DOACs were candidates for administration of antiviral agents (lopinavir, ritonavir, or darunavir). Plasma samples for DOAC measurement were collected 2to 4 days after starting antiviral treatment, at 12 hours from the last dose intake in patients on dabigatran and apixaban, and at 24 hours in those on rivaroxaban and edoxaban. For each patient, C‐trough DOAC level, expressed as ng/mL, was compared with the one measured before hospitalization. ResultsOf the 1039 patients hospitalized between February 22 and March 15, 2020 with COVID‐19 pneumonia and candidates for antiviral therapy, 32 were on treatment with a DOAC. DOAC was stopped in 20 and continued in the remaining 12. On average, C‐trough levels were 6.14 times higher during hospitalization than in the pre‐hospitalization period. ConclusionDOAC patients treated with antiviral drugs show an alarming increase in DOAC plasma levels. In order to prevent bleeding complications, we believe that physicians should consider withholding DOACs from patients with SARS‐CoV‐2 and replacing them with alternative parenteral antithrombotic strategies for as long as antiviral agents are deemed necessary and until discharge.

Bivalirudin Versus Heparin During Intervention in Acute Coronary Syndrome: A Systematic Review of Randomized Trials.

Introduction: Bivalirudin and heparin are the two most commonly used anticoagulants used during Percutaneous Coronary Intervention (PCI). The results of Randomized Controlled Trials (RCTs) comparing bivalirudin versus heparin monotherapy in the era of radial access are controversial, questioning the positive impact of bivalirudin on bleeding. The purpose of this systematic review is to summarize the results of RCTs comparing the efficacy and safety of bivalirudin versus heparin with or without Glycoprotein IIb/IIIa Inhibitors (GPI).Methods:This systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA statements for reporting systematic reviews. We searched the National Library of Medicine PubMed, Clinicaltrial.gov and the Cochrane Central Register of Controlled Trials to include clinical studies comparing bivalirudin with heparin in patients undergoing PCI. Sixteen studies met inclusion criteria and were reviewed for the summary.Findings: Several RCTs and meta-analyses have demonstrated the superiority of bivalirudin over heparin plus routine GPI use in terms of preventing bleeding complications but at the expense of increased risk of ischemic complications such as stent thrombosis. The hypothesis of post- PCI bivalirudin infusion to mitigate the risk of acute stent thrombosis has been tested in various RCTs with conflicting results. In comparison, heparin offers the advantage of having a reversible agent, of lower cost and reduced incidence of ischemic complications.Conclusion:Bivalirudin demonstrates its superiority over heparin plus GPI with better clinical outcomes in terms of less bleeding complications, thus making it as anticoagulation of choice particularly in patients at high risk of bleeding. Further studies are warranted for head to head comparison of bivalirudin to heparin monotherapy to establish an optimal heparin dosing regimen and post-PCI bivalirudin infusion to affirm its beneficial effect in reducing acute stent thrombosis.